CN102596268B - The coating adhesive composition of soft tissue adhesive composition, wound or wound coating composition - Google Patents

Abstract

Soft tissue adhesive composition of the present invention, the coating adhesive composition of wound or wound coating composition, the soft tissue adhesive composition containing monomer (A), polymer (B) and the polymerization initiator composition (C) containing organoboron compound, the coating adhesive composition of wound or wound coating composition, it is characterized in that, above-mentioned (A), (B) and (C) mix viscosity within latter 30 seconds in the scope of 0.4 ~ 75,000cp.Above-mentioned composition of the present invention not only toxicity and harmfulness low, have high bonding strength, and operability during coating is excellent, the characteristic of the film of formation is also excellent.

Description

The coating adhesive composition of soft tissue adhesive composition, wound or wound coating composition

Technical field

The present invention relates to soft tissue adhesive composition, the coating adhesive composition of wound or wound coating composition.

Background technology

All the time, as coating binding agent or the wound coating agent of soft tissue adhesives, wound site, the compositions of cyanoacrylate and the compositions containing fibrin are such as contained to multiple combination thing and is studied (such as, see patent documentation 1 and patent documentation 2) containing compositionss etc. employed from the material of organism such as albuminous compositionss.

When the compositions containing cyanoacrylate, although bonding strength large in excellent, but lack biocompatible, the formaldehyde that the hydrolysis of its solidfied material generates demonstrates larger toxicity to organism, hinder and cure, there is larger problem, especially can not use at the position directly contacted with nervus centralis, blood vessel etc.In addition, because hardening time is extremely short, so be sometimes difficult to use.

When containing the compositions from the material of organism, although good at biocompatible, not easily hinder in healing excellent, but bonding strength is little, and, especially when the compositions containing fibrin is used as binding agent etc., also deposit the fibrin contained in the composition and stick with paste the problem becoming the culture medium this respect of antibacterial, exist after surgery or dispose the rear danger occurring to infect, its harmfulness that fears are entertained that.

In addition, when binding agent being used for wound site or the soft tissues etc. such as skin, or when wound site uses wound coating agent, consider operability, protect from infection, usually in container etc., compositions is prepared in each composition mixing in advance, then, said composition is applied to soft tissue, surface that wound is coated to position etc.Such as, but mixed state brings impact for operability during coating composition sometimes, if the viscosity of compositions is too high, be difficult to coating, or, if viscosity is too low, outside trickling to necessary position etc.And then, the characteristic of the film (i.e. film) that if binding agent or wound coating agent are polymerized, be solidified to form, if such as elasticity, tensile elongation are improper, then due to the adherend that skin, soft tissue etc. are soft, so sometimes cause film from problems such as skin peelings after coating.

In addition, use the acrylic adhesives of the initiator containing organoboron compound due to toxicity and harmfulness low, there is high bonding strength, so be just widely used in gear division purposes (such as with reference to patent documentation 3.)。But, when wanting to be coated to purposes etc. for other medical applications such as surgical use, soft tissue bonding purposes, wound, sometimes expect to improve further after mixing until be applied to Treatment Stability and the operability of the compositions of application site.

Patent documentation 1: Japanese Unexamined Patent Publication 2007-061658

Patent documentation 2: Japanese Unexamined Patent Publication 2006-051121

Patent documentation 3: Japanese Unexamined Patent Publication 9-110913

Summary of the invention

The object of the present invention is to provide a kind of compositions, described compositions not only toxicity and harmfulness low, there is high bonding strength, and operability excellence during coating, the characteristic of the film formed by said composition is suitable for use as soft tissue binding agent, the coating binding agent of wound or wound coating agent.

The present inventor etc. are in order to solve above-mentioned problem, and for being suitable for use as soft tissue binding agent, wound is coated to and repeatedly conducts in-depth research by the compositions of binding agent or wound coating agent.Found that, utilize following adhesive composition or wound coating composition, above-mentioned problem can be solved, thus complete the present invention, described adhesive composition or wound coating composition contain monomer, polymer and specific polymerization initiator composition, and their mixed viscosity is in specific scope.It should be noted that, soft tissue adhesive composition of the present invention, the coating adhesive composition of wound or Wound covering material compositions, refer to by coating the wound portion that produces on the soft tissues such as the skin of organism, muscle, internal organs and blood vessel due to operation, accident etc. namely from disconnected tissue surface, by the adhering skin in wound portion and the compositions of the material temporarily wound portion is coated to.

Namely, soft tissue adhesive composition of the present invention, wound are coated to and are by the feature of adhesive composition or wound coating composition, containing monomer (A), polymer (B) and the polymerization initiator composition (C) containing organoboron compound, above-mentioned (A), (B) and (C) mix viscosity within latter 30 seconds in the scope of 0.4 ~ 75,000cp.

Above-mentioned polymer (B) is preferably following polymeric blends: relative to the gross weight of polymer particle (b1), (b2) and (b3), polymer particle (b2) containing more than 2 % by weight and polymer particle (b3), less than 0 ~ 98 % by weight polymer particle (b1) (total amount of (b1), (b2) and (b3) is 100 % by weight), the weight average molecular weight of polymer particle (b2) is 5 × 10 ⁴~ 20 × 10 ⁴and specific surface area is 0.51 ~ 1.2 (m ²/ g), the weight average molecular weight of polymer particle (b3) is 5 × 10 ⁴~ 20 × 10 ⁴and specific surface area is 0.1 ~ 0.5 (m ²/ g), the weight average molecular weight of polymer particle (b1) is 30 × 10 ⁴~ 60 × 10 ⁴and specific surface area is 1.5 ~ 4.5 (m ²/ g).

For at the above-mentioned adhesive composition of preparation or wound coating composition after 24 hours, thick more than 0.1 μm that is obtained by said composition, long more than 25mm and the film of wide more than 2mm, modulus of elasticity in static bending when preferably measuring under the condition of test speed 2mm/ minute is below 750MPa, further, tensile elongation when measuring under condition for test speed 1mm/ minute is more than 5%.

Above-mentioned adhesive composition or wound coating composition still can contain such as polymerization inhibitor (D), UV absorbent, plasticizer etc.

Preferably relative to monomer (A), the content of the polymerization inhibitor (D) in above-mentioned composition is in the scope of 10 ~ 5000ppm.

As above-mentioned polymerization inhibitor (D), preferably be selected from hydroquinone, dibutyl hydroquinone, Hydroquinone monomethylether, 2, at least one in 6-DI-tert-butylphenol compounds, 2,6 ditertiary butyl p cresol, catechol, 1,2,3,-thrihydroxy-benzene, benzoquinone, 2-hydroxyl benzoquinone, p methoxy phenol, tert-butyl catechol, butylated hydroxyanisol, Yoshinox BHT and tertiary butylated hydroquinone.

In addition, above-mentioned adhesive composition or wound coating composition also can containing at least one be selected from following substances: anti-infective, antibiotic, antibacterial, antiviral agent, analgesic, the coordination compound of analgesic, appetite suppressant, vermifuge, anti-arthritic, anti-asthmatic, spasmolytic, antidepressants, antidiuretic, diarrhea, antihistaminic, anti-inflammatory agent, migraine medicament, antiemetic, antineoplastic agent, antiparkinsonism drug, antipruritic, psychosis, antipyretic, anti-spasmodics, anticholinergic, sympathetic activation agent, cardiovascular drugs agent, anti-arrhythmic, antihypertensive, diuretic, vasodilation, immunosuppressant, muscle relaxant, parasympatholytic, analeptic, tranquilizer, spiritual stability agent, cholinomimetic, chemotherapeutics, radiopharmaceutical, self-bone grafting medicine, the heparin nertralizer (heparin neutralizer agents of static bladder) of bladder quiescence, coagulant, hemorrhage, xanthine derivative, hormone, natural origin or the protein synthesized by genetic engineering, polysaccharide, glycoprotein, lipoprotein, oligonucleotide, antibody, antigen, vassopressin, vassopressin analog, epinephrine, select albumen, the courageous and upright poisonous substance of coagulant, plasminogen activator inhibitor, platelet activating agent, and there is the synthetic peptide of anastalsis, and

The spice such as orange oil, Oleum Citri grandis, Fructus Citri Limoniae oil, white lemon oil (lime oil), Oleum Caryophylli, wintergreen oil, Oleum menthae, peppermint spirit, Fructus Musae distillation, Fructus Cucumidis sativi distillation, Mel distillation, rose water, menthol, anethole, alkyl salicylate, benzaldehyde, monosodium glutamate, ethyl vanillin, thymol and vanillin.

The feature being coated to the test kit used with binding agent or wound coating agent as soft tissue binding agent, wound of the present invention is to have as lower member: the monomer (A) contained by above-mentioned adhesive composition or wound coating composition, polymer (B) and polymerization initiator composition (C) each composition containing organoboron compound are divided into more than two parts with combination in any and they are received.

Mentioned reagent box preferably has following formation: monomer (A), polymer (B) and polymerization initiator composition (C) are independently received, first monomer (A) and the polymerization initiator composition (C) containing organoboron compound are mixed, then mixed polymer (B).

When mentioned reagent box contains polymerization inhibitor (D), described test kit has as lower member: soft tissue adhesive composition, wound be coated to and be divided into more than two parts with the monomer (A) contained by adhesive composition or wound coating composition, (methyl) acrylate polymer (B), polymerization initiator composition (C) containing organoboron compound and polymerization inhibitor (D) each composition with combination in any and they received.

In the mentioned reagent box containing polymerization inhibitor, preferably there is following formation: the mixture of monomer (A) and polymerization inhibitor (D), polymer (B) and polymerization initiator composition (C) are independently received, first monomer (A) is mixed with the mixture of polymerization inhibitor (D) and the polymerization initiator composition (C) containing organoboron compound, following mixed polymer (B).

In mentioned reagent box, the instrument that uses when also can comprise the following compositions of coating, described compositions is mixed to get containing above-mentioned (A), (B), (C) and the adhesive ingredients of composition contained further as required or wound coating agent composition.

As above-mentioned instrument, such as pen, fibrous nodules, cloth, sponge ball, sponge sheet etc. can be enumerated.

In mentioned reagent box, still can comprise the bonding pre-treatment aqueous solution of citric acid and 1 ~ 5 % by weight iron chloride (III) containing 1 ~ 15 % by weight.

Soft tissue adhesive composition of the present invention, the coating adhesive composition of wound or wound coating composition, not only toxicity and harmfulness low, there is high bonding strength, and operability excellence during coating said composition, the characteristic of the film formed by said composition is suitable for use as soft tissue bonding, the coating bonding of wound, wound coating agent.In addition, when above-mentioned composition is applied to wound site, binding agent can bond wound portion securely.Especially, when above-mentioned composition of the present invention is applied to crust wound site, crust wound can be made to engage, and after healing, this binding agent is peeled off naturally from crust.

Accompanying drawing explanation

[Fig. 1] schematic diagram of the preparation method of sample film for using in example embodiments of the invention.

[Fig. 2] is for evaluating the schematic diagram of the preparation method of the assess sample of bonding strength in example embodiments of the invention 14A ~ 17A.

[Fig. 3] is for evaluating the schematic diagram of the preparation method of the assess sample of bonding strength in example embodiments of the invention 1C, 3C, 4C, 17C.

Detailed description of the invention

Containing monomer (A) in soft tissue adhesive composition of the present invention, the coating adhesive composition of wound or wound coating composition.As monomer (A), just can use without particular limitation as long as following polymerization initiator composition (C) can be utilized to carry out polymerization.In addition, as monomer (A), according to application target, monofunctional monomer, polyfunctional monomer all can use.

As above-mentioned monomer (A), methacrylate, acrylate and other vinyl compounds etc. can be enumerated.

In these monomers (A), consider to the stimulation lower one face of human body, preferred acrylate and methacrylate, wherein more preferably acrylate and methacrylate (below, are referred to as (methyl) acrylate by methacrylate sometimes.)。

In addition, in monomer (A), excellent from the viewpoint of cohesive, preferably there is the monomer of acidic-group.

Therefore, as monomer (A), also preferably (methyl) acrylate (wherein not having acidic-group) and the combination of monomers with acidic-group are carried out the scheme used.

As simple function (methyl) acrylate (wherein not there is acidic-group), such as (methyl) acrylic acid methyl ester. can be enumerated, (methyl) ethyl acrylate, (methyl) propyl acrylate, (methyl) butyl acrylate, (methyl) Hexyl 2-propenoate, (methyl) acrylic acid-2-ethyl hexyl ester, (methyl) dodecylacrylate, (methyl) lauryl acrylate, (methyl) cyclohexyl acrylate, (methyl) benzyl acrylate, (methyl) alkyl acrylates such as (methyl) isobornyl acrylate,

(methyl) acrylic acid 2-hydroxyethyl ester, (methyl) acrylic acid 2-hydroxy-propyl ester, (methyl) acrylic acid 3-hydroxy-propyl ester, (methyl) acrylic acid 4-hydroxybutyl ester, (methyl) acrylic acid 5-Hydroxy pentyl ester, (methyl) acrylic acid 6-Hydroxyhexyl, list (methyl) acrylic acid 1, (methyl) acrylic acid hydroxyalkyl acrylates such as 2-dihydroxypropyl ester, list (methyl) acrylic acid 1,3-dihydroxypropyl ester, list (methyl) acrylic acid erithritol ester;

Polyalkylene glycol mono (methyl) acrylate such as diglycol monotertiary (methyl) acrylate, 2,2'-ethylenedioxybis(ethanol). list (methyl) acrylate, polyethyleneglycol (methyl) acrylate, polypropylene glycol list (methyl) acrylate;

(gathering) alkylene glycol monoalkyl ethers (methyl) acrylate such as ethylene glycol monomethyl ether (methyl) acrylate, ethylene glycol monomethyl ether (methyl) acrylate, diethylene glycol monomethyl ether (methyl) acrylate, triethylene glycol monomethyl ether (methyl) acrylate, MPEG-550 (methyl) acrylate, polypropylene glycol monoalky lether (methyl) acrylate;

(methyl) acrylic acid fluoroalkyl esters such as (methyl) perfluoroethyl octyl group ester, (methyl) acrylic acid hexafluoro butyl ester;

γ-(methyl) acryloxypropyl trimethoxy silane, γ-(methyl) acryloxypropyl three (trimethylsiloxy) silane etc. have the silane compound of (methyl) acryloxyalkyl; And

(methyl) tetrahydrofurfuryl acrylate etc. has (methyl) acrylate etc. of heterocycle.

As multifunctional (methyl) acrylate (wherein not there is acidic-group), many (methyl) acrylate of the alkane polyols such as such as ethylene glycol bisthioglycolate (methyl) acrylate, propylene glycol two (methyl) acrylate, butanediol two (methyl) acrylate, neopentyl glycol two (methyl) acrylate, hexanediol two (methyl) acrylate, trimethylolpropane tris (methyl) acrylate, tetramethylolmethane four (methyl) acrylate can be enumerated;

Polyoxy base alkane polyol many (methyl) acrylate such as diethylene glycol two (methyl) acrylate, 2,2'-ethylenedioxybis(ethanol). two (methyl) acrylate, Polyethylene Glycol two (methyl) acrylate, dipropylene glycol two (methyl) acrylate, polypropylene glycol two (methyl) acrylate, dibutylene glycol two (methyl) acrylate, dipentaerythritol six (methyl) acrylate;

The alicyclic ring class that following formula (1) represents or aromatic series two (methyl) acrylate,

(in above-mentioned formula (1), R represents hydrogen atom or methyl, m and n can be identical or different, represents the number of 0 ~ 10, R ¹represent

In any one.)；

The alicyclic ring class that following formula (2) represents or aromatic epoxies two (methyl) acrylate,

(in above-mentioned formula (2), R represents hydrogen atom or methyl, and n represents the number of 0 ~ 10, R ¹represent

In any one.); And

Multifunctional (methyl) acrylate of what following formula (3) represented have in the molecule amino-formate bond,

(in above-mentioned formula (3), R represents hydrogen atom or methyl, R ²represent

In any one.)；

Deng.

In above-mentioned (methyl) acrylate, as simple function (methyl) acrylate, preferably (methyl) alkyl acrylate such as (methyl) acrylic acid methyl ester., (methyl) ethyl acrylate;

(methyl) acrylic acid hydroxyalkyl acrylates such as (methyl) acrylic acid 2-hydroxyethyl ester, list (methyl) acrylic acid 1,3-dihydroxypropyl ester, list (methyl) acrylic acid erithritol ester;

Polyethyleneglycol (methyl) acrylate etc. such as triethylene glycol monomethyl ether (methyl) acrylate, 2,2'-ethylenedioxybis(ethanol). list (methyl) acrylate.

In addition, as multifunctional (methyl) acrylate, preferred 2,2'-ethylenedioxybis(ethanol). two (methyl) acrylate, Polyethylene Glycol two (methyl) acrylate etc. have two (methyl) acrylate of glycol chain in molecule;

The compound that following formula (1)-a represents,

(in formula (1)-a, R represents hydrogen atom or methyl, m and n can be identical or different, represents the number of 0 ~ 10.)；

The compound that following formula (2)-a represents,

(in above-mentioned formula (2)-a, R represents hydrogen atom or methyl.); And

The compound that following formula (3)-a represents,

(in above-mentioned formula (3)-a, R represents hydrogen atom or methyl.) etc.

Above-mentioned (methyl) acrylate can be used alone or combine two or more use.

As the monomer with acidic-group, (methyl) acrylic acid and anhydride thereof can be enumerated such as, Isosorbide-5-Nitrae-two (methyl) acryloyl-oxyethyl PMA, 6-(methyl) acryloyl-oxyethyl naphthalene 1,2,6-tricarboxylic acid, N-(methyl) acryloyl group para-amino benzoic acid, N-(methyl) acryloyl group ortho-aminobenzoic acid, N-(methyl) acryloyl group gavaculine, N-(methyl) acryloyl group-5-aminosalicylic acid, N-(methyl) acryloyl group-4-ASA, 4-(methyl) acryloyl-oxyethyl trimellitic acid and anhydride thereof, 4-(methyl) acryloxy butyl trimellitic acid and anhydride thereof, 4-(methyl) acryloxy hexyl trimellitic acid and anhydride thereof, 4-(methyl) acryloxy decyl trimellitic acid and anhydride thereof, 2-(methyl) acryloyl group p-methoxybenzoic acid, 3-(methyl) acryloyl group p-methoxybenzoic acid, 4-(methyl) acryloyl group p-methoxybenzoic acid, succinic acid β-(methyl) acryloyl group oxygen base ethyl ester, maleic acid β-(methyl) acryloyl group oxygen base ethyl ester, phthalic acid β-(methyl) acryloyl group oxygen base ethyl ester, 11-(methyl) acryloyl group Oxy-1,1-undecane, vinyl benzoic acid etc. is had to the monomer of carboxyl or its anhydride group,

(2-(methyl) acryloyl-oxyethyl) phosphoric acid, (2-(methyl) acryloyl-oxyethyl phenyl) phosphoric acid, 10-(methyl) acryloxy decylphosphonic acid etc. have the monomer of phosphate; And

P styrene sulfonic acid, 2-acrylamide-2-methyl propane sulfonic etc. have sulfonic monomer etc.

Have in the monomer of acidic-group above-mentioned, preferred 4-methacryloxyethyl trimellitic acid and anhydride thereof.

The above-mentioned monomer with acidic-group can be used alone or combine two or more use.By using the above-mentioned monomer with acidic-group, soft tissue adhesive composition of the present invention, wound are coated to exists by the cohesive of adhesive composition or wound coating composition the tendency improved further.

For the above-mentioned monomer with acidic-group, relative to above-mentioned (methyl) acrylate (wherein not there is acidic-group) and monomer total amount 100 weight portion with acidic-group, preferably containing 1 ~ 20 weight portion, more preferably 1 ~ 10 weight portion, the more preferably amount of 1 ~ 8 weight portion.When not in above-mentioned scope, sometimes give bonding strength or harmful effect is brought to the adaptability of organism.

For the addition of above-mentioned monomer (A), relative to monomer (A) and following polymer (B) and polymerization initiator composition (C) total amount 100 weight portion, preferably 10 ~ 98.95 weight portions, more preferably 25 ~ 89.5 weight portions, more preferably 37 ~ 86 weight portions.

When the above-mentioned scope of addition deficiency of monomer (A), there is viscosity to uprise, be coated with the tendency becoming difficulty.When the addition of monomer (A) exceedes above-mentioned scope, lack bonding force, so mixture may trickle to target site hinder treatment.

For the addition of above-mentioned monomer (A), also comprise following situation: relative to monomer (A) and following polymer (B) and polymerization initiator composition (C) total amount 100 weight portion, preferably 5 ~ 98.95 weight portions, more preferably 17 ~ 98.5 weight portions, more preferably 20 ~ 85 weight portions, particularly preferably 24 ~ 85 weight portions, further preferred 24 ~ 48 weight portions.

When the above-mentioned scope of addition deficiency of monomer (A), viscosity uprises, and there is the tendency that coating waits operation change difficulty.When the addition of monomer (A) exceedes above-mentioned scope, there is the tendency that the physical property such as bonding strength and the modulus of elasticity in static bending, hot strength, bending strength is deteriorated.And then mixture may trickle to target site, hinder treatment.

Also containing polymer (B) in soft tissue adhesive composition of the present invention, the coating adhesive composition of wound or wound coating composition.

As above-mentioned polymer (B), such as methacrylate polymers, acrylate polymer, styrenic elastomer, polyvinyl chloride-base elastomer, olefin type elastomer, polyester elastomer, polyamide-based elastomer and carbamates elastomer, ethylene vinyl acetate copolymer, organosilicon polymer etc. can be enumerated.They can be used alone or combine two or more use.

In above-mentioned polymer (B), from the viewpoint of homogeneity during mixing, preferred methacrylate polymer and acrylate polymer.Below, sometimes methacrylate polymers and acrylate polymer are referred to as (methyl) acrylate polymer.)。

As above-mentioned (methyl) acrylate polymer, the such as non-cross-linked polymer such as poly-(methyl) acrylic acid methyl ester., poly-(methyl) ethyl acrylate, (methyl) acrylic acid methyl ester. (methyl) ethyl acrylate copolymer, (methyl) acrylic acid methyl ester. (methyl) butyl acrylate copolymer, (methyl) acrylic acid methyl ester. styrol copolymer can be enumerated;

The cross linked polymers etc. such as the copolymer of (methyl) acrylic acid methyl ester. ethylene glycol bisthioglycolate (methyl) acrylate copolymer, (methyl) acrylic acid methyl ester. 2,2'-ethylenedioxybis(ethanol). two (methyl) acrylate copolymer, (methyl) acrylic acid methyl ester. and butadiene type monomer.

It should be noted that, in above-mentioned polymer, by the elastomers such as the rubber such as natural rubber, synthetic rubber, thermoplastic elastomer (TPE) and (methyl) acrylate polymer is used in combination, can be used as softening agent plays a role, and can improve the flexibility of compositions.As synthetic rubber, such as EPT (EPT) etc. can be enumerated.As above-mentioned thermoplastic elastomer (TPE), such as styrenic elastomer, polyvinyl chloride-base elastomer, olefin type elastomer, polyester elastomer, polyamide-based elastomer and carbamates elastomer, ethylene vinyl acetate copolymer, organosilicon polymer etc. can be enumerated.

Above-mentioned elastomeric molecular weight is generally 1000 ~ 1,000,000, preferably 2000 ~ 500,000.In addition, above-mentioned elastomeric vitrification point (Tg) is generally less than 20 DEG C, is preferably less than 0 DEG C.

And then, in above-mentioned (methyl) acrylate polymer, also containing the organic mineral complex that metal-oxide or slaine are coated to by above-mentioned non-cross-linked polymer or cross linked polymer.

The weight average molecular weight of above-mentioned polymer, representational (methyl) acrylate polymer preferably 1000 ~ 1,000,000 scope, the more preferably scope of 50,000 ~ 500,000, the more preferably scope of 100,000 ~ 500,000.It should be noted that, above-mentioned molecular weight is the molecular weight of the standard that the is scaled polymethyl methacrylate utilizing gel permeation chromatography (GPC) to obtain.

In addition, above-mentioned polymer (B) can be polymer particle.When polymer (B) is the polymer beads period of the day from 11 p.m. to 1 a.m, it can be multiple polymers particle.

As above-mentioned polymer particle, such as weight average molecular weight 30 × 10 can be enumerated ⁴~ 60 × 10 ⁴and specific surface area 1.5 ~ 4.5 (m ²/ g) polymer particle (b1), weight average molecular weight 5 × 10 ⁴~ 20 × 10 ⁴and specific surface area 0.51 ~ 1.2 (m ²/ g) polymer particle (b2), weight average molecular weight 5 × 10 ⁴~ 20 × 10 ⁴and specific surface area 0.1 ~ 0.5 (m ²/ g) polymer particle (b3).

The specific surface area of above-mentioned polymer particle (b1) is preferably 1.5 ~ 4.5 (m ²/ g), be more preferably 2.0 ~ 4.0 (m ²/ g).

The specific surface area of above-mentioned polymer particle (b2) is preferably 0.51 ~ 1.2 (m ²/ g), be more preferably 0.6 ~ 1.0 (m ²/ g).

The specific surface area of above-mentioned polymer particle (b3) is preferably 0.1 ~ 0.5 (m ²/ g), be more preferably 0.2 ~ 0.45 (m ²/ g).

The volume average particle size of above-mentioned polymer particle (b1) is generally 1 ~ 50 (μm), is preferably 5 ~ 40 (μm).The volume average particle size of above-mentioned polymer particle (b2) is generally 0.1 ~ 40 (μm), is preferably 1 ~ 20 (μm).The volume average particle size of above-mentioned polymer particle (b3) is generally 1 ~ 50 (μm), is preferably 5 ~ 40 (μm).

When polymer (B) is the polymeric blends be made up of above-mentioned polymer particle (b2) and polymer particle (b3) and the polymer particle (b1) that uses as required, relative to the gross weight of polymer particle (b1), polymer particle (b2) and polymer particle (b3), (b2) and the total amount of (b3) be preferably more than 2 % by weight, more preferably more than 5 % by weight.It should be noted that also there is the situation that above-mentioned polymeric blends is made up of polymer particle (b2) and polymer particle (b3) total amount 100 % by weight.

When polymer particle (b2) and (b3) total amount are more than above-mentioned lower limit, polymer (B) is easy to dispersed in monomer (A), the dissolubility of polymer (B) in monomer (A) is more excellent, moreover, compositions also becomes easier to the coating of wound portion, soft tissue etc., and the compositions of depositing after coating also becomes less tendency in wound portion or sprawling of soft tissue surfaces.

When polymer particle comprises polymer particle (b1), relative to the gross weight of polymer particle (b1), polymer particle (b2) and polymer particle (b3), polymer particle (b2) and (b3) total amount are preferably less than 99 % by weight, be more preferably less than 95 % by weight, be more preferably less than 90 % by weight.

When polymer particle comprises polymer particle (b1), relative to the gross weight of polymer particle (b1), polymer particle (b2) and polymer particle (b3), the content of polymer particle (b1) is preferably less than 98 % by weight, is more preferably less than 95 % by weight.In addition, relative to the gross weight of polymer particle (b1), polymer particle (b2) and polymer particle (b3), the content of polymer particle (b1) is preferably more than 1 % by weight, be more preferably more than 5 % by weight, be more preferably more than 10 % by weight.

Relative to monomer (A), polymer (B) and polymerization initiator composition (C) total amount 100 weight portion, the addition of above-mentioned polymer (B) is preferably 1 ~ 70 weight portion, be more preferably 10 ~ 65 weight portions, be more preferably 13 ~ 65 weight portions, more preferably 13 ~ 60 weight portions.

When the above-mentioned scope of addition deficiency of polymer (B), polymerization is difficult to carry out, and lacks bonding effect, and mixture may flow out to outside target site and hinder treatment.When the addition of polymer (B) exceeds above-mentioned scope, exist and become difficulty with mixing of monomer (A) and cause extruding from container the tendency becoming difficulty because viscosity sharply rises.In addition, polymerization is sometimes carried out, and rapidly forms polymerizing curable thing, exists as the unexcellent tendency of the operability of binding agent or wound coating agent.

In addition, when above-mentioned polymer (B) is (methyl) acrylate polymer, relative to monomer (A), (methyl) acrylate polymer and following polymerization initiator composition (C) total amount 100 weight portion, its addition is preferably 1 ~ 75 weight portion, it is more preferably 1 ~ 73 weight portion, be more preferably 10 ~ 73 weight portions, more preferably 15 ~ 73 weight portions, be particularly preferably 13 ~ 68 weight portions, most preferably be 21 ~ 64 weight portions.

When the above-mentioned scope of addition deficiency of (methyl) acrylate polymer, there is the tendency reduced in the physical property such as bonding strength and the modulus of elasticity in static bending, hot strength, comprcssive strength, bending strength.When the addition of (methyl) acrylate polymer exceeds above-mentioned scope, viscosity uprises, and there is the tendency that the operations such as coating, injection become difficulty.

In addition, when polymer (B) be (methyl) acrylate polymer, mixture for above-mentioned polymer particle (b1), (b2) and (b3) time, under polymer particle (b1), (b2) and (b3) total amount are 100 % by weight and (b2) and (b3) total amount is the condition of more than 2 % by weight, preferably more than 5 % by weight, preferably following scheme.

Relative to monomer (A), polymer (B) and polymerization initiator composition (C) 100 weight portion, polymer (B) is in the above scope less than 28 weight portions of 13 weight portions, polymer particle (b1) is preferably 10 % by weight ~ 95 % by weight, be more preferably 15 % by weight ~ 95 % by weight, be more preferably 38 % by weight ~ 95 % by weight, polymer particle (b2) is preferably less than 90 % by weight, be more preferably less than 85 % by weight, be more preferably less than 62 % by weight, polymer particle (b3) is preferably less than 90 % by weight, be more preferably less than 85 % by weight, be more preferably less than 62 % by weight,

Relative to monomer (A), polymer (B) and polymerization initiator composition (C) 100 weight portion, polymer (B) is in the above scope less than 68 weight portions of 28 weight portions, polymer particle (b1) is preferably 10 % by weight ~ 95 % by weight, be more preferably 10 % by weight ~ 80 % by weight, be more preferably 10 % by weight ~ 60 % by weight, polymer particle (b2) is preferably less than 90 % by weight, polymer particle (b3) is preferably less than 80 % by weight, is more preferably less than 75 % by weight;

Relative to monomer (A), polymer (B) and polymerization initiator composition (C) 100 weight portion, polymer (B) is in the above scope less than 68 weight portions of 33 weight portions, polymer particle (b1) is preferably less than 10 % by weight, be more preferably less than 8 % by weight, be more preferably less than 5 % by weight, polymer particle (b2) is preferably less than 100 % by weight, be more preferably 20 % by weight ~ 100 % by weight, polymer particle (b3) is preferably less than 100 % by weight, is more preferably less than 80 % by weight.

Soft tissue adhesive composition of the present invention, wound are coated to and are to use the following initiator composition (C) containing organoboron compound (c1) by the feature of adhesive composition or wound coating composition, if organoboron compound is added in the compositions containing monomer, then polyreaction is comparatively early namely the stage slowly starts, carry out polyreaction, on the other hand, when using peroxide as polymerization initiator, even if mixed polymerization initiator, until polymerization starts also to need the long period.Polyreaction is once being quick response, and within a short period of time completes, and has a great difference in this.Therefore, in order to form the compositions being suitable for wound portion, soft tissue etc., relative to more than monomer (A) stating the amount of bright mistake to use polymer of the present invention (B) to be important.By using described polymer (B), not only can guarantee operability for a long time, and the mobility, the coating that are suitable for wound portion, soft tissue etc. can be guaranteed.

Soft tissue adhesive composition of the present invention, wound to be coated to the polymerization initiator composition (C) contained by adhesive composition or wound coating composition containing organoboron compound (c1) as required composition, can contain non-protonic solvent (c2), alcohol (c3) as required.By comprising the above-mentioned polymerization initiator composition (C) containing organoboron compound (c1) in above-mentioned composition of the present invention, when said composition being coated wound portion, soft tissue etc. and said composition is all solidified, monomer (A) residual also tends to more less as the situation of the compositions of polymerization initiator than employing peroxide.And then a part infiltrates into epithelium, initiated polymerization.Therefore, above-mentioned composition of the present invention is suitable for organism.

As organoboron compound (c1), such as trialkylboron, alkoxyalkyl boron, Dialkylborane and partial oxidation trialkylboron etc. can be enumerated.

As trialkylboron, such as boron triethyl, tripropylborane, triisopropyl boron, tri butyl boron, three sec-butyl boron, triisobutylboron, three amyl group boron, three hexyl boron, three heptyl boron, trioctylphosphine boron, three cyclopenta boron, thricyclohexyl boron etc. can be enumerated there is the trialkylboron that carbon number is the alkyl of 2 ~ 8.It should be noted that, abovementioned alkyl can be any one in straight chained alkyl, branched alkyl, cycloalkyl, and 3 alkyl contained in trialkylboron can be the same or different.

As alkoxyalkyl boron, there are monoalkoxy dialkyl group boron, dialkoxy monoalkyl boron etc.As above-mentioned alkoxyalkyl boron, the monoalkoxy dialkyl group boron such as such as butoxy dibutyl boron can be enumerated.It should be noted that, the moieties of the alkyl that alkoxyalkyl boron has and this alkoxyl can be the same or different.

As Dialkylborane, such as dicyclohexyl borane, diisoamyl borine etc. can be enumerated.It should be noted that, two alkyl that Dialkylborane has can be the same or different.In addition, two alkyl contained in above-mentioned Dialkylborane can form single ring architecture or twin nuclei by bonding.As described compound, 9-borabi cyclo [3.3.1] nonane (9-borabicyclo [3.3.1] nonane) etc. can be enumerated.

Partial oxidation trialkylboron refers to the partial oxide of above-mentioned trialkylboron.As this partial oxidation trialkylboron, preferred partial oxidation tri butyl boron.In addition, as partial oxidation trialkylboron, can use and add preferably 0.3 ~ 0.9 mole, the more preferably oxygen of 0.4 ~ 0.6 mole and the material that formed relative to 1 mole of trialkylboron.

In above-mentioned organoboron compound, preferred tri butyl boron or partial oxidation tri butyl boron, more preferably partial oxidation tri butyl boron.When tri butyl boron, partial oxidation tri butyl boron being used as organoboron compound (c1), not only operability improves, and existence has suitable reactive tendency relative to the organism with moisture.In addition, when tri butyl boron, partial oxidation tri butyl boron are used as organoboron compound (c1), even if because the washy place reaction such at organism also can start and carry out, so monomer is difficult to the interface remaining in binding agent or wound coating agent and organism, therefore few to the hazardness of organism.Above-mentioned organoboron compound (c1) can be used alone or combine two or more use.

Still non-protonic solvent (c2) can be contained in polymerization initiator composition (C).Like this, owing to being diluted containing non-protonic solvent, organoboron compound in polymerization initiator composition (C), so the exothermicity with flammable organoboron compound (c1) becomes more stable and suppresses flammable, during carrying, when preserving, mixing time process become easy.In addition, the suitable reduction due to exothermicity can to suppress when using the binding agent of huge amount or wound coating agent heat release sharply, so have to the damage of the tissue contacted with binding agent of the present invention or wound coating agent the tendency diminished.Above-mentioned non-protonic solvent (c2) boiling point is at 1 atmosphere pressure generally 30 DEG C ~ 150 DEG C, is preferably 50 DEG C ~ 120 DEG C.When the not enough above-mentioned scope of boiling point, when carrying or in preserving, can occur that non-protonic solvent volatilize from polymerization initiator composition, the situation such as to disperse, there is the tendency of reduction in the inhibition on fire of organoboron compound (c1).In addition, when boiling point exceeds above-mentioned scope, the residual change of non-protonic solvent on the solidfied material formed by adhesive composition of the present invention or wound coating composition is many, and the bond properties of compositions has the tendency of reduction.

As above-mentioned non-protonic solvent (c2), preferably do not react, can be formed the solvent of homogeneous solution with organoboron compound (c1).

As non-protonic solvent (c2), the hydrocarbon such as such as pentane, hexane, cyclohexane extraction, heptane, benzene, toluene can be enumerated;

The halogenated hydrocarbons such as fluorobenzene, 1,1-dichloroethanes, 1,2-dichloroethanes, said flon;

The ethers such as ether, Di Iso Propyl Ether, ethylene glycol dimethyl ether, oxolane;

The ketone such as acetone, methyl ethyl ketone, metacetone; And

The esters etc. such as methyl acetate, ethyl acetate, isopropyl acetate.

Wherein, saturated aliphatic hydrocarbon, ether and the esters such as preferred pentane, hexane, heptane, more preferably hexane, Di Iso Propyl Ether, ethyl acetate.

Above-mentioned non-protonic solvent (c2) can be used alone or combine two or more use.

Relative to organoboron compound (c1) 100 weight portion, the content of the non-protonic solvent (c2) in above-mentioned polymerization initiator composition (C) is preferably 30 ~ 80 weight portions.

When non-protonic solvent (c2) containing quantity not sufficient above-mentioned scope time, can not get sufficient dilution effect, there is heat release or the insufficient tendency of inhibition on fire.On the other hand, when the content of non-protonic solvent (c2) exceedes above-mentioned scope, the polymerization initiating power that there is polymerization initiator composition (C) is reduced to the tendency that can not satisfy the demand.

In polymerization initiator composition (C), except non-protonic solvent (c2), alcohol (c3) can also be contained further.By adding a small amount of alcohol (c3) in polymerization initiator composition (C), can when not reducing polymerization activity, the reaction depending on organoboron compound (c1) is more stably carried out, easily suppresses to be charred or tendency on fire even if exist to contact with paper etc. in atmosphere also to become.

As alcohol (c3), such as methanol, ethanol, normal propyl alcohol and isomer, n-butyl alcohol and isomer, n-amyl alcohol and isomer, hexanol and isomer, n-heptanol and isomer thereof etc. can be enumerated.

In above-mentioned alcohol (c3), preferred carbon number is the alcohol of less than 4, that is, methanol, ethanol, normal propyl alcohol and isomer thereof and n-butyl alcohol and isomer, more preferably ethanol and normal propyl alcohol.

Above-mentioned alcohol (c3) can be used alone or combine two or more use.

Relative to organoboron compound (c1) 100 weight portion, the content of the alcohol (c3) in above-mentioned polymerization initiator composition (C) is preferably 0.2 ~ 5 weight portion, be more preferably 0.3 ~ 4.5 weight portion, be more preferably 0.5 ~ 4 weight portion.

When alcohol (c3) containing quantity not sufficient above-mentioned scope time, can not get sufficient dilution effect, there is heat release or the insufficient tendency of inhibition on fire.On the other hand, when the content of alcohol (c3) exceedes above-mentioned scope, the polymerization initiating power that there is polymerization initiator composition (C) is reduced to the tendency that can not satisfy the demand.

In addition, when to use alcohol (c3) and non-protonic solvent (c2) simultaneously, relative to organoboron compound (c1) 100 weight portion, the content of the non-protonic solvent (c2) in above-mentioned polymerization initiator composition (C) is preferably 5 ~ 40 weight portions, be more preferably 10 ~ 30 weight portions, be more preferably 10 ~ 25 weight portions.

When non-protonic solvent (c2) relative to organoboron compound (c1) 100 weight portion containing quantity not sufficient above-mentioned scope time, there is heat release or the insufficient tendency of inhibition on fire.On the other hand, when the content of non-protonic solvent (c2) exceedes above-mentioned scope relative to organoboron compound (c1) 100 weight portion, the tendency that the polymerization initiating power that there is polymerization initiator composition (C) reduces.

Relative to total amount 100 weight portion of monomer (A), polymer (B) and polymerization initiator composition (C), the addition of above-mentioned polymerization initiator composition (C) is preferably 0.05 ~ 20 weight portion, be more preferably 0.5 ~ 10 weight portion, be more preferably 1 ~ 3 weight portion.

When the above-mentioned scope of addition deficiency of polymerization initiator composition (C), polymerization becomes and is difficult to carry out, and there is the tendency lacking bonding effect.When the addition of polymerization initiator composition (C) exceedes above-mentioned scope, because dilution makes viscosity to reduce, harmful effect may be brought to safety.In addition, assuming that polymerization sharply forms rapidly polymerizing curable thing, so exist as the unexcellent tendency of the operability of binding agent or wound coating agent.

In above-mentioned adhesive composition or wound coating composition, bringing in dysgenic scope to its performance, also can contain other compositions further as required.

As an example of other compositions, polymerization inhibitor (D) can be enumerated.As above-mentioned polymerization inhibitor (D), hydroquinone compound class, the Hydroquinone monomethylether, 2 such as hydroquinone, dibutyl hydroquinone can be enumerated, the phenol such as 6-DI-tert-butylphenol compounds, 2,6 ditertiary butyl p cresol, catechol, 1,2,3,-thrihydroxy-benzene, benzoquinone, 2-hydroxyl benzoquinone, p methoxy phenol, tert-butyl catechol, butylated hydroxyanisol, Yoshinox BHT and tertiary butylated hydroquinone etc.Wherein, the mixture of Hydroquinone monomethylether and 2,6 ditertiary butyl p cresol is preferably used.

In above-mentioned polymerization inhibitor (D), have good stability from the viewpoint of himself, sometimes preferred Hydroquinone monomethylether.

Above-mentioned polymerization inhibitor (D) can be used alone or combine two or more use.

When adding above-mentioned polymerization inhibitor (D), relative to adhesive composition or wound coating composition total amount, preferably add 10 ~ 5000ppm polymerization inhibitor (D), more preferably 50 ~ 1000ppm, more preferably 50 ~ 500ppm.

In addition, relative to above-mentioned monomer (A), preferably above-mentioned polymerization inhibitor (D) is added with the scope of 10 ~ 5000ppm.

By forming such compositions, such as, compared with the past, during the adherend such as affected part (affected part moist due to the transudate from cut etc.), wound site, soft tissue when binding agent being applied to surgical operation, guarantee coating and excellent in suitable hardening time, can be used as binding agent and coating agent stably operates.And operability is excellent.

The addition of above-mentioned polymerization inhibitor (D) is described above, but more preferably adds with the scope of 50 ~ 1000ppm, more preferably 50 ~ 500ppm relative to monomer (A).By forming above-mentioned composition, such as, exist and not only stably can to process when set of applications compound but also can the tendency of hardening composition efficiently after application.When the scope above-mentioned containing quantity not sufficient of polymerization inhibitor (D), namely solidify after monomer (A), polymer (B) and polymerization initiator (C) just mixing, there is the tendency that coating becomes difficulty.On the other hand, when the content of polymerization inhibitor (D) exceedes above-mentioned scope, there is the tendency making the polymerization initiating power of polymerization initiator composition (C) reduce, unnecessarily extend, be difficult to use in hardening time medical application.

As an example of other compositions, UV absorbent can be enumerated further.As above-mentioned UV absorbent, such as 2-(2 '-hydroxyl-5 '-aminomethyl phenyl) benzotriazole can be enumerated, 2-(3 ', 5 '-di-t-butyl-2 '-hydroxy phenyl) benzotriazole, 2-(5 '-tert-butyl group-2 '-hydroxy phenyl) benzotriazole, 2-(2 '-hydroxyl-5 '-(1, 1, 3, 3-tetramethyl butyl) phenyl) benzotriazole, 2-(3 ', 5 '-di-t-butyl-2 '-hydroxy phenyl)-5-chlorobenzotriazole, 2-(3 '-tert-butyl group-2 '-hydroxyl-5 '-aminomethyl phenyl)-5-chlorobenzotriazole, 2-(3 '-sec-butyl-5 '-the tert-butyl group-2 '-hydroxy phenyl) benzotriazole, 2-(2 '-hydroxyl-4 '-octyloxyphenyl) benzotriazole, 2-(3 ', 5 '-two tertiary pentyl-2 '-hydroxy phenyl) benzotriazole, 2-(3 ', 5 '-bis-(α, α-dimethylbenzyl)-2 '-hydroxy phenyl) benzotriazole, 2-(3 '-tert-butyl group-2 '-hydroxyl-5 '-(2-octyl group oxygen base carbonylethyl) phenyl)-5-chlorobenzotriazole, 2-(3 '-tert-butyl group-5 '-[2-(2-ethylhexyl oxygen base) carbonylethyl]-2 '-hydroxy phenyl)-5-chlorobenzotriazole, 2-(3 '-tert-butyl group-2 '-hydroxyl-5 '-(2-dion e) phenyl)-5-chlorobenzotriazole, 2-(3 '-tert-butyl group-2 '-hydroxyl-5 '-(2-dion e) phenyl) benzotriazole, 2-(3 '-tert-butyl group-2 '-hydroxyl-5 '-(2-octyl group oxygen base carbonylethyl) phenyl) benzotriazole, 2-(3 '-tert-butyl group-5 '-[2-(2-ethylhexyl oxygen base) carbonylethyl]-2 '-hydroxy phenyl) benzotriazole, 2-(3 '-dodecyl-2 '-hydroxyl-5 '-aminomethyl phenyl) benzotriazole, 2-(3 '-tert-butyl group-2 '-hydroxyl-5 '-(2-iso-octyl oxygen base carbonylethyl) phenyl) benzotriazole and 2, 2 '-di-2-ethylhexylphosphine oxide [4-(1, 1, 3, 3-tetramethyl butyl)-6-benzotriazole-2-base phenol] mixture, the ester exchange reaction product of 2-[3 '-tert-butyl group-5 '-(2-dion e)-2 '-hydroxy phenyl] benzotriazole and Liquid Macrogol, [[R-CH ₂cH ₂-COOCH ₂] ₃] ₂the benzotriazole cpds such as-(in formula, R=3 '-tert-butyl group-4 '-hydroxyl-5 '-2H-benzotriazole-2-base phenyl),

2,4-dihydroxy benaophenonel, ESCALOL 567,2-hydroxyl-4-octyloxybenzophenone, 2-hydroxyl-4-decyl oxygen base benzophenone, 2-hydroxyl-4-dodecyl oxygen base benzophenone, 2-hydroxyl-4-behzyloxybenzophenone, 2,2 ', 4,4 '-tetrahydroxybenzophenone and 2, the benzophenone cpds such as 2 '-dihydroxy-4,4 '-dimethoxy-benzophenone;

Salicylic acid 4-tert-butyl-phenyl ester, phenyl salicylate, bigcatkin willow octylphenyl salicylate, dibenzoyl resorcinols, two (4-tert-butyl-benzoyl) resorcinol, benzoyl resorcinol, 3,5-di-tert-butyl-4-hydroxybenzoic acid 2,4-di-tert-butyl-phenyl ester, 3,5-di-tert-butyl-4-hydroxybenzoic acid cetyl ester, 3,5-di-tert-butyl-4-hydroxybenzoic acid stearyl and benzoic acid 2-methyl-4,6-di-tert-butyl-phenyl ester;

Decanedioic acid two (2, 2, 6, 6-tetramethyl-piperidyl) ester, succinic acid two (2, 2, 6, 6-tetramethyl-piperidyl) ester, decanedioic acid two (1, 2, 2, 6, 6-pentamethvl base) ester, two (1, 2, 2, 6, 6-pentamethvl base) normal-butyl-3, 5-di-tert-butyl-4-hydroxyl benzyl malonate, 1-hydroxyethyl-2, 2, 6, the condensation product of 6-tetramethyl-4-hydroxy piperidine and succinic acid, N, N '-bis-(2, 2, 6, 6-tetramethyl-4-piperidyl) hexamethylene diamine and the tertiary octyl amino-2 of 4-, 6-bis-chloro-1, 3, the condensation product of 5-s-triazine, three (2, 2, 6, 6-tetramethyl-4-piperidyl) nitrilotriacetate, four (2, 2, 6, 6-tetramethyl-4-piperidyl)-1, 2, 3, 4-butane four ester (butanetetraoate), 1, 1 '-(1, 2-ethylidene) two (3, 3, 5, 5-tetramethyl piperazinones), 4-benzoyl-2, 2, 6, 6-tetramethyl piperidine, 4-stearyl oxygen base (stearyloxy)-2, 2, 6, 6-tetramethyl piperidine, two (1, 2, 2, 6, 6-pentamethyl-4-piperidyl) 2-normal-butyl-2-(2-hydroxyl-3, 5-di-t-butyl benzyl) malonate, 3-n-octyl-7, 7, 9, 9-tetramethyl-1, 3, 8-thriazaspiro [4.5] decane-2, 4-diketone, two (the 1-octyl group oxygen base-2 of decanedioic acid, 2, 6, 6-tetramethyl-piperidyl) ester, two (the 1-octyl group oxygen base-2 of succinic acid, 2, 6, 6-tetramethyl-piperidyl) ester, N, N '-bis-(2, 2, 6, 6-tetramethyl-4-piperidyl) hexamethylene diamine and 4-morpholino-2, 6-bis-chloro-1, 3, the condensation product of 5-triazine, 2-chloro-4, 6-bis-(4-n-butylamino-2, 2, 6, 6-tetramethyl-piperidyl)-1, 3, 5-triazine and 1, the condensation product of two (3-amino propyl amino) ethane of 2-, 2-chloro-4, 6-bis-(4-n-butylamino-1, 2, 2, 6, 6-pentamethvl base)-1, 3, 5-triazine and 1, the condensation product of two (3-amino propyl amino) ethane of 2-, 8-acetyl group-3-dodecyl-7, 7, 9, 9-tetramethyl-1, 3, 8-thriazaspiro [4.5] decane-2, 4-diketone, and 3-dodecyl-1-(2, 2, 6, 6-tetramethyl-4-piperidyl) pyrrolidine-2, 5-diketone, and 3-dodecyl-1-(1, 2, 2, 6, 6-pentamethyl-4-piperidyl) pyrrolidine-2, the hindered amine compounds such as 5-diketone,

4, 4 '-dioctyloxyoxanilide, 2, 2 '-diethoxy butoxanilide, 2, 2 '-dioctyl oxygen base-5, 5 '-di-t-butyl butoxanilide, 2, 2 '-bis-dodecyl oxygen base-5, 5 '-di-t-butyl butoxanilide, 2-ethyoxyl-2 '-ethyloxanilide, N, N '-bis-(3-dimethylaminopropyl) oxamides, 2-ethyoxyl-5-the tert-butyl group-2 '-ethyloxanilide and 2-ethyoxyl-2 '-ethyl-5, the mixture of 4 '-di-t-butyl butoxanilide, adjacent and to methoxyl group-, and it is adjacent and ethyoxyl-two is replaced to the oxalamide compound such as mixture of butoxanilide,

2, 4, 6-tri-(2-hydroxyl-4-octyl group oxygen base phenyl)-1, 3, 5-triazine, 2-(2-hydroxyl-4-octyl group oxygen base phenyl)-4, 6-two (2, 4-3,5-dimethylphenyl)-1, 3, 5-triazine, 2-(2, 4-dihydroxy phenyl)-4, 6-two (2, 4-3,5-dimethylphenyl)-1, 3, 5-triazine, 2, two (2-hydroxyl-4-propyl group oxygen base the phenyl)-6-(2 of 4-, 4-3,5-dimethylphenyl)-1, 3, 5-triazine, 2-(2-hydroxyl-4-octyl group oxygen base phenyl)-4, two (the 4-aminomethyl phenyl)-1 of 6-, 3, 5-triazine, 2-(2-hydroxyl-4-dodecyl oxygen base phenyl)-4, 6-two (2, 4-3,5-dimethylphenyl)-1, 3, 5-triazine, 2-[2-hydroxyl-4-(2-hydroxyl-3-butyl oxygen base propyl group oxygen base) phenyl]-4, 6-two (2, 4-3,5-dimethylphenyl)-1, 3, 5-triazine, 2-[2-hydroxyl-4-(2-hydroxyl-3-octyl group oxygen base propyl group oxygen base) phenyl]-4, 6-two (2, 4-3,5-dimethylphenyl)-1, 3, 5-triazine, and 2-[4-dodecyl/tridecyl oxygen base-(2-hydroxypropyl) oxygen base-2-hydroxy phenyl]-4, 6-two (2, 4-3,5-dimethylphenyl)-1, 3, the 2-(2-hydroxy phenyl)-1 such as 5-triazine, 3, 5-triaizine compounds,

Such as, triphenyl phosphite, diphenylalkyl phosphites, phenyldialkyl phosphites, three (nonylphenylphosphite), trilauryl phosphite, three (octadecyl) phosphite ester, distearyl pentaerythrityl diphosphite, three (2,4-di-tert-butyl-phenyl) phosphite ester, diiso decyl pentaerythritol diphosphites, two (2,4-di-tert-butyl-phenyl) pentaerythritol diphosphites, two (2,6-di-t-butyl-4-aminomethyl phenyl) pentaerythritol diphosphites, two isodecyl oxygen base pentaerythritol diphosphites, two (2,4-, bis--tert-butyl group-6-aminomethyl phenyl) pentaerythritol diphosphites, two (2,4,6-tri-tert phenyl) pentaerythritol diphosphites, three stearyl sorbitol phosphite esters, four (2,4-di-tert-butyl-phenyls) 4,4 '-biphenylen, 6-iso-octyl oxygen base-2,4,8,10-tetra--tert-butyl group-12H-dibenzo [d, g]-1,3,2-dioxy phospha eight ring, fluoro-2,4,8, the 10-tetra-tert-12-methyldiphenyls of 6-are [d, g]-1,3,2-dioxy phospha eight ring also, bi-ester of phosphite or the phosphinate compounds etc. such as two-(2,4-di-t-butyl-6-aminomethyl phenyl) methylisothiouronium methylphosphite ester and two (2,4-di-t-butyl-6-aminomethyl phenyl) ethide phosphite ester.

As above-mentioned UV absorbent, preferred benzotriazole cpd.

When adding above-mentioned UV absorbent, relative to monomer (A), preferably add 10 ~ 1,000ppm, more preferably 100 ~ 800ppm.By adding UV absorbent like this, the liquid color containing monomer can be suppressed, there is the tendency of the storage stability improving monomer itself.

As an example of other compositions, plasticizer can be enumerated further.

As above-mentioned plasticizer, the hydroxycarboxylic acid esters such as citrate, 1-Hydroxy-1,2,3-propanetricarboxylic acid. ester, tartrate, malate, lactate, monoglyceride and glycolic acid esters can be enumerated; Tri trimellitate methyl ester, dibenzoic diglycol laurate, diethyl malonate, adjacent acetyl citrate triethyl group ester, benzyl butyl phthalate, dibenzoic acid dipropylene glycol ester, ethyl adipate, adjacent acetyl citrate tributyl ester, dimethyl sebacate and aklylene glycol diester etc.

The addition of above-mentioned plasticizer suitably can be selected according to the kind of material, usually following use: in adhesive composition or wound coating composition total amount, usually containing 0 ~ 30wt%, preferably 0 ~ 20wt%, more preferably 0 ~ 10wt%.

As an example of other compositions, antiseptic can be enumerated further.

As foregoing preservatives, methyl parahydroxybenzoate, Sodium Methyl Hydroxybenzoate, ethylparaben, propyl p-hydroxybenzoate, Sodium Propyl Hydroxybenzoate, butyl p-hydroxybenzoate can be enumerated;

Cresol, chlorocresol;

Resorcinol, 4-n-hexyl resorcinol, 3a, 4,7,7a-tetrahydrochysene-2-((trichloromethyl) sulfenyl)-1H-iso-indoles-1,3 (2H)-diketone; Benzalkonium chloride, benzalkonium chloride sodium (benzalkonium sodium chloride), benzethonium chloride;

Merphenyl, the formaldehyde etc. such as benzoic acid, benzylalcohol, cetylpyridinium chloride, methaform, dehydroactic acid, o-phenyl phenol, phenol, phenethanol, Potassium Benzoate, potassium sorbate, sodium benzoate, dehydro sodium acetate, sodium propionate, sorbic acid, thimerosal, thymol, phenylmercuric borate, phenylmercuric nitrate and phenylmercuric acetate.

As an example of other compositions, anti-infective can be enumerated further, antibiotic, antibacterial, antiviral agent, analgesic, the coordination compound of analgesic, appetite suppressant, vermifuge, anti-arthritic, anti-asthmatic, spasmolytic, antidepressants, antidiuretic, diarrhea, antihistaminic, anti-inflammatory agent, migraine medicament, antiemetic, antineoplastic agent, antiparkinsonism drug, antipruritic, psychosis, antipyretic, anti-spasmodics, anticholinergic, sympathetic activation agent, cardiovascular drugs agent, anti-arrhythmic, antihypertensive, diuretic, vasodilation, immunosuppressant, muscle relaxant, parasympatholytic, analeptic, tranquilizer, spiritual stability agent, cholinomimetic, chemotherapeutics, radiopharmaceutical, self-bone grafting medicine, the heparin nertralizer of bladder quiescence, coagulant, hemorrhage, xanthine derivative, hormone, natural origin or the protein synthesized by genetic engineering, polysaccharide, glycoprotein, lipoprotein, oligonucleotide, antibody, antigen, vassopressin, vassopressin analog, epinephrine, select albumen, the courageous and upright poisonous substance of coagulant, plasminogen activator inhibitor, platelet activating agent, and there is the synthetic peptide etc. of anastalsis.It should be noted that, by containing mentioned component, compositions of the present invention also can be used for drug-supplying system and regenerative medicine purposes.

As above-mentioned antibacterial, elemental iodine, solid povidone iodine, povidone iodine can be enumerated;

Tribromphenol, trichlorophenol, 2,4,6,-T, tetrachlorophenol, nitrophenol, 3-methyl-4-chlorophenol, 3, 5-dimethyl-4-chlorophenol, phenyl phenol, dichlorophen, o-phenyl phenol, between phenylphenol, 4-hydroxydiphenyl, 2-benzyl-4-chlorophenol, 2, 4-bis-chloro-3, 5-xylenol, 4-chlorothymol, benzyl chlorophenol, triclosan, fenticlor, phenol, 2-methylphenol, 3-methylphenol, 4-methylphenol, 4-ethyl-phenol, 2, 4-xylenol, 2, 5-xylenol, 3, 4-xylenol, 2, 6-xylenol, 4-n-pro-pyl phenol, 4-normal-butyl phenol, 4-n-pentyl phenol, 4-tert-amyl phenol, 4-n-hexyl phenol, 4-n-heptyl phenol, monoalkyl halophenol, many alkyl halophenol, aromatic series halophenol, and ammonium salt, the oxybenzene compound such as alkali metal salt and alkali salt,

Silver nitrate, hexachlorophene, merbromin, tetracycline HCl, tetracycline hydrate and erythromycin etc.

It should be noted that, in above-mentioned adhesive composition or wound coating composition, as above-mentioned protein, also can further containing by the angiogenesis factor, basic fibroblast growth factor, epidermal growth factor etc. that promote for the purpose of tissue repair etc.

As an example of other compositions above-mentioned, the spice such as orange oil, Oleum Citri grandis, Fructus Citri Limoniae oil, white lemon oil, Oleum Caryophylli, wintergreen oil, Oleum menthae, peppermint spirit, Fructus Musae distillation, Fructus Cucumidis sativi distillation, Mel distillation, rose water, menthol, anethole, alkyl salicylate, benzaldehyde, monosodium glutamate, ethyl vanillin, thymol and vanillin can be enumerated further.

In addition, as an example of other compositions, also inorganic filler, organic filler, organic composite filler, filler coloring agent etc. can be contained further.

As inorganic filling material, the metal oxide powders such as such as Zirconium oxide, bismuth oxide, titanium oxide, zinc oxide, aluminium oxide particles can be enumerated;

The metal salt powders such as waltherite, zirconium phosphate, barium sulfate;

Quartz glass, containing lead glass, containing barium glass, containing glass fillers such as strontium glass, Zirconium orthosilicate. glass; There is the filler of silver-colored slow-releasing; And there is the filler etc. of fluorine slow-releasing.

It should be noted that, firmly combining from the viewpoint of being formed between inorganic filling material after hardening and monomer (A), preferably use and implemented the surface-treated such as silane treatment, polymer-coated inorganic filling material.

Above-mentioned inorganic filling material can be used alone or combine two or more use.

In addition, as an example of other compositions, the x-ray contrast agent such as barium sulfate, zirconium oxide etc. can be enumerated.As above-mentioned x-ray contrast agent, preferential oxidation zirconium in the present invention.

Soft tissue adhesive composition of the present invention, wound are coated to and are by the feature of adhesive composition or wound coating composition, above-mentioned (A), (B), (C) and contain as required composition mixing latter 30 seconds within viscosity in the scope of 0.4 ~ 75,000cp.

By making viscosity in above-mentioned scope, be easy to coating as binding agent or wound coating agent.

From the viewpoint of operability, mobility, above-mentioned viscosity preferably in the scope of 0.4 ~ 10,000cp, more preferably 1 ~ 10,000cp scope in.

In addition, for adhesive composition of the present invention or wound coating composition, above-mentioned (A), (B), (C) and the composition contained as required mix the viscosity of latter 60 seconds preferably 10 ~ 1, in the scope of 000,000cp, more preferably 20 ~ 1,000, in the scope of 000cp, more preferably in 30cp ~ 800, in the scope of 000cp.

By making viscosity in above-mentioned scope, as binding agent or wound coating agent, can easily extrude from container, and the operability being easy to the aspects such as coating is excellent.

Compositions of the present invention is excellent as coatings such as the operability of binding agent or wound coating agent and mobility.In addition, with using peroxide compared with the compositions that initiator composition uses, there is the tendency that operator can guarantee the time of being longer than the time of carrying out required for married operation, operability is also excellent in this.

At preparation above-mentioned adhesive composition of the present invention or wound coating composition after 24 hours, obtain having more than 1 μm, preferably below 1cm thickness and the film of long more than 25mm, wide more than 2mm by said composition, for above-mentioned film, the modulus of elasticity in static bending when measuring under condition for test speed 2mm/ minute is preferably below 750MPa, be more preferably below 740MPa, be more preferably below 730MPa.In addition, preparing above-mentioned composition after 24 hours, obtain having more than 1 μm, preferably below 1cm thickness and the film of long more than 25mm, wide more than 2mm by said composition, for above-mentioned film, the modulus of elasticity in static bending when measuring under condition for test speed 2mm/ minute is preferably below 750MPa, be more preferably below 600MPa, be more preferably below 550MPa.

In addition, the modulus of elasticity in static bending of above-mentioned firming body is preferably more than 100MPa, is more preferably more than 150MPa, is more preferably more than 200MPa.

In addition, at preparation above-mentioned adhesive composition of the present invention or wound coating composition after 24 hours, obtain having more than 1 μm, preferably below 1cm thickness and the film of wide more than the 2mm of long more than 25mm by said composition, for this film, tensile elongation when measuring under condition for test speed 1mm/ minute is preferably more than 5%, be more preferably more than 15%, be more preferably more than 25%.

In addition, above-mentioned tensile elongation can be preferably more than 5%, is more preferably more than 7%, is more preferably more than 9%.And then above-mentioned tensile elongation can preferably more than 30%, is more preferably more than 40%, is more preferably more than 50%.

The solidfied material obtained by above-mentioned adhesive composition of the present invention or wound coating composition is excellent in the physical property of the coated film (film) for soft tissue and skin, carries out stretching, the cohesive of bending position etc. is excellent for the bending position on skin and joint etc.

In the present invention, in advance above-mentioned monomer (A), polymer (B), polymerization initiator composition (C) and other composition mixing contained as required can be prepared adhesive composition or wound coating composition, said composition be coated the places such as wound site (affected part during surgical operation, wound are coated to position), soft tissue and use.

It should be noted that, when by above-mentioned each composition mixing, order by merging is not limited, but from the viewpoint of Absorbable organic halogens mixing equably, preferably first by monomer (A) and polymerization initiator composition (C) mixing, following mixed polymer (B).

In addition, when adhesive composition of the present invention or wound coating composition contain polymerization inhibitor (D), more excellent from the viewpoint of the stability of the compositions making to obtain, preferably first the mixture of monomer (A) and polymerization inhibitor (D) and polymerization initiator composition (C) are mixed, then mixed polymer (B).

In addition, before adhesive composition of the present invention or wound coating composition are solidified or in solidification process, the electromagnetic waves such as visible ray, ionizing ray (such as gamma-rays), electron beam can be irradiated further and carry out sterilization processing.It should be noted that, the viewpoint that never makes condition of cure significantly change is considered, sometimes also preferred radiation of visible light.In addition, xeothermic, gas, the process of filtering, utilizing liquid etc., the autoclave sterilization treatment etc. such as steam, oxirane (EO), hydrogen peroxide also can be utilized to carry out sterilization processing.

In addition, also before adhesive composition of the present invention or wound coating composition are coated on wound site, soft tissue etc., can carry out disinfection with the surface of the disinfectant solution such as alcohol to wound site, soft tissue etc. in advance.

And then, before adhesive composition of the present invention or wound coating composition are coated on the position such as wound site, soft tissue, for improving the objects such as cohesive, also can pre-treatment be carried out.As above-mentioned pretreatment liquid, such as, can enumerate the aqueous solution etc. of iron chloride (III) of citric acid and 1 ~ 5 % by weight containing 1 ~ 15 % by weight.

When adhesive composition of the present invention or wound coating composition are coated wound portion, described compositions is polymerized and is solidified to form film, such as forms film like, therefore can be used for bonding wound portion, coating wound face (namely, can use like this: after making edge of wound be combined, by adhesive coated in wound portion surface, with surface adhesive and solidify).In addition, in order to fix, protect the end of above-mentioned membranaceous firming body or entirety, maintenance, strengthen bonding force, when be coated with to wound site, soft tissue surfaces etc. or after being coated with, the coating articles for use such as film, lamella or paper, rubber plaster, binder, gauze can also be used.Above-mentioned coating articles for use can have cohesive, also can have zygosity.

And then, when wound portion application alginate lining material, hydrogel and hydropolymer or after application, also can be coated with above-mentioned adhesive composition or wound coating composition.

When worry adhesive composition of the present invention or wound coating composition are due to long-term preservation, take care of and form or performance change occur, when impairing effect of the present invention, can will comprise monomer (A), polymer (B), each composition of other compositions contained as required such as polymerization initiator composition (C) and polymerization inhibitor (D) is received separately or is accommodated in plural parts with combination in any segmentation, formed as soft tissue binding agent, the coating binding agent of wound, or the test kit that wound coating agent uses, preserve with described kit form and carry out before use mixing to form above-mentioned adhesive composition or wound coating composition.As above-mentioned storage parts, in order to prevent being vaporized of monomer (A) or polymerization initiator composition (C), disperse, the sealable plastic holding device or glass syringe (syringe) etc. such as with barrier properties for gases can be enumerated.As the parts for receiving polymer (B), airtight good resin and the glass container for preventing moisture absorption can be enumerated.Its storage is measured, has the situation use amount be once finished being accommodated in container and the situation of nonexpondable amount being received.

As preserving the method for above-mentioned each composition, the method that the mixture, (B) and the mixture of other compositions contained as required and three parts, the mixture of (C) and other compositions contained as required that are such as divided into (A) and other compositions contained as required carry out preserving can be enumerated; Be divided into the method that (A), the mixture of (B) and other compositions contained as required and (C) two parts carry out preserving; Two parts, the mixture of the mixture and (C) and other compositions contained as required that are divided into (A) and (B) carries out the method for preserving; Be divided into the method that (A), (B) and the mixture of a part of other compositions contained as required and two parts, the mixture of the remainder of (C) and other compositions contained as required carry out preserving; Two parts, the mixture of the mixture and (B) and (C) that are divided into (A) and other compositions contained as required carries out the method for preserving; Be divided into (A) and (B), two parts, the mixture of (C) and other compositions contained as required carries out the method for preserving; Be divided into the mixture of a part for (A) and other compositions contained as required and (B), two parts, the mixture of remainder of (C) and other compositions contained as required carries out the method etc. of preserving.

In addition, when containing polymerization inhibitor (D), can enumerate such as be divided into (A) and other compositions contained as required mixture, the mixture of (B) and other compositions contained as required, (C) and other compositions contained as required three parts, mixture carry out the method for preserving; Be divided into the method that (A), (B), the mixture of (D) and other compositions contained as required and (C) two parts carry out preserving; Be divided into the method that (A), the mixture of (B) and (D) and two parts, the mixture of (C) and other compositions contained as required carry out preserving; Be divided into the method that (A), (B), (D) and the mixture of a part of other compositions contained as required and two parts, the mixture of the remainder of (C) and other compositions contained as required carry out preserving; Be divided into the method that (A), (D) and the mixture of other compositions contained as required and two parts, the mixture of (B) and (C) carry out preserving; Be divided into the mixture of (A) and (D) and (B), two parts, the mixture of (C) and other compositions contained as required carries out the method for preserving; Be divided into (A), the mixture of a part of (D) and other compositions contained as required and (B), two parts, the mixture of remainder of (C) and other compositions contained as required carries out the method etc. of preserving.

It should be noted that, as monomer (A), when using containing when there is the monomer of acidic-group and not there is the mixture of monomer of acidic-group, except above-mentioned store method, the method that the state that the monomer that also can utilize not make to have acidic-group contacts with polymerization initiator composition carries out preserving is preserved, such as, the method that monomer, the mixture of (B) and other compositions contained as required and two parts, the mixture of the monomer and (C) without acidic-group with acidic-group carry out preserving is divided into; Two parts, the mixture of the mixture being divided into monomer and (B) with acidic-group and the monomer without acidic-group, (C) and other compositions contained as required carries out the method for preserving; Two parts, the mixture of the mixture being divided into monomer and other compositions contained as required with acidic-group and the monomer without acidic-group, (B) and (C) carries out the method for preserving; Be divided into the monomer with acidic-group and the monomer without acidic-group, (B), (C) and other compositions contained as required two parts, mixture carry out the method etc. of preserving.

The above-mentioned material being divided into two parts can load the containers etc. such as respective parts, such as syringe, and storage is coated in the test kit used with binding agent or wound coating agent provides to as soft tissue binding agent, wound with product form.

For mentioned reagent box, as long as no due to keeping, form or performance change, hinder the danger of effect of the present invention to be just not particularly limited its formation, but preferred following formation: monomer (A), polymer (B) and polymerization initiator composition (C) are independently received, first monomer (A) and the polymerization initiator composition (C) containing organoboron compound are mixed, then mixed polymer (B).By being above-mentioned formation, easily obtain adhesive composition or the wound coating composition with more stable performance.

As mentioned reagent box, the parts (such as container, syringe etc.) that such as have and independently receive monomer (A), polymer (B) and polymerization initiator composition (C) can be enumerated and for they being taken out from their parts of storage and the test kit of the parts mixed (such as mixer, mix ware etc.);

Monomer (A), polymer (B) and polymerization initiator composition (C) are independently accommodated in the room of more than 3 be separated at a container inner-use clapboard, monomer (A) and the path of polymerization initiator composition (C) by arranging in syringe is in advance made, the test kit etc. with agitating unit mixed with polymer (B) by destruction dividing plate or moveable partition board.

In addition, when mentioned reagent box contains polymerization inhibitor (D), preferably be constructed as follows: independently receive the mixture, polymer (B) and the polymerization initiator composition (C) that contain monomer (A) and polymerization inhibitor (D), first will mix containing monomer (A) and the mixture of polymerization inhibitor (D) and the polymerization initiator composition (C) containing organoboron compound, then mixed polymer (B).By being such formation, easily obtain having the soft tissue binding agent of more stable performance, the coating binding agent of wound or wound coating agent.

As mentioned reagent box, can enumerate such as there is the independently mixture of storage containing monomer (A) and polymerization inhibitor (D), polymer (B) and polymerization initiator composition (C) parts (such as, container, syringe etc.) and for they being taken out from their parts of storage and the test kit of the parts mixed (such as, mixer, mixing ware etc.);

Mixture containing monomer (A) and polymerization inhibitor (D), polymer (B) and polymerization initiator composition (C) are independently accommodated in the room of more than 3 be separated at a container inner-use clapboard, the mixture containing monomer (A) and polymerization inhibitor (D) and polymerization initiator composition (C) is made to pass through the path arranged in syringe in advance, the test kit etc. with agitating unit mixed with polymer (B) by destroying dividing plate or moveable partition board.

With compositions of the present invention is deposited in respectively in plural parts such as container, and being about to carry out mixing the method used and compare when using, time saving and energy saving by the test kit formed at the above-mentioned container being separated into each composition of indoor storage of more than 3, and, only take out the compositions of necessary amount from container and make it directly contact with the instrument such as sponge and not use mixer etc., can use economically thus.

In addition, part or all that also can make polymerization initiator composition (C) composition is in advance contained in the instrument used when adhesive composition or wound coating composition being coated wound site, soft tissue etc., being about to make monomer (A) or the mixture containing monomer (A) and polymerization inhibitor (D), polymer (B) and other compositions contained as required contact with instrument when using, prepare adhesive composition of the present invention or wound coating composition then and there, directly coat wound site, soft tissue etc.

As the instrument be coated with to wound site, soft tissue etc., such as pen, fibrous nodules, cloth, sponge ball, sponge sheet etc. can be enumerated.

It should be noted that, mentioned reagent box also can comprise the disinfectant solution such as above-mentioned alcohol, to improve the solution for pre-treatment for the purpose of cohesive etc., coating articles for use etc.

In addition, when preserving with above-mentioned test kit, can, preferably under the condition of each components unchanged matter (such as, monomer does not solidify), the electromagnetic waves etc. such as visible ray be utilized to carry out sterilization treatment.

Soft tissue adhesive composition of the present invention, wound be coated to adhesive composition or wound coating composition can be used for the closing of such as wound site, the biological tissue such as protection, inaccessible, fixing (bonding) soft tissue graft sheet, hemostasis, vascular anastomosis, vascular occlusion, bronchus are coincide, bronchus is inaccessible, ophthalmologic operation bonds.

In addition, for above-mentioned composition of the present invention, by it directly being coated the wound of the crust such as skin, mucosa being formed at organism, easily can engage the peristome etc. in wound portion, in addition, when skin transplantation, also can be used for graft to be fixed on transplantation site etc.

It should be noted that, when above-mentioned composition of the present invention is used as the coating binding agent of wound, following use usually: do not coat wound surface, and after edge of wound is combined, by adhesive coated in surface, wound portion, be cured with surface adhesive.On the other hand, when abrading or the wound portion in face is not cut in crush injury, contusion etc., also directly can coat affected part and carrying out coating wound.

Embodiment

Below, specifically describe the present invention further by embodiment, but the present invention is not by the restriction of these embodiments.

(embodiment 1A ~ 18A)

(reagent)

In embodiment, as monomer (A), polymer (B) and polymerization initiator composition (C), use following material.

Monomer (A): the methyl methacrylate solution (weight ratio about 5%) of 4-META/MMA:4-methacryloxyethyl trimellitic acid anhydride

Polymer (B): 3 kinds of following PMMA (polymethyl methacrylate) (b1) ~ (b3) and pigment mixture.Relative to above-mentioned 3 kinds of PMMA and pigment total amount 100 weight portion, weight ratio is respectively (b1) 20.03 weight portions, (b2) 62.5 weight portion, (b3) 12.5 weight portion, surplus is pigment.

PMMA (the b1) ~ molecular weight of (b3), character are as described below.

(b1) weight average molecular weight: 450,000; Volume average particle size: 26.7 μm;

Specific surface area: 2.913m ²/ g

(b2) weight average molecular weight: 140,000; Volume average particle size: 8.2 μm;

Specific surface area: 0.827m ²/ g

(b3) weight average molecular weight: 140,000; Volume average particle size: 24.6 μm;

Specific surface area: 0.371m ²/ g

It should be noted that, the volume average particle size of PMMA (refractive index 1.49) measures as follows: use reagent superfine methanol (refractive index 1.33) (with light pure pharmaceutical worker's industry Inc.) as dispersion solvent, disperse 5 minutes (power 25W) with the built-in ultrasonic homogenizer of device, under the concentration conditions of device Loading Index in proper range, with circulation rate 50% (when 100%, 65ml/ second), use Microtrac MT3300EXII (Microtrac Inc. particle size distribution meter) to measure.

In addition, specific surface area is the value using BET method to measure, and is use Autosorb 3 (Quantachrome Inc.), is tried to achieve by the nitrogen adsorption of (77K) under liquid nitrogen temperature.

Polymerization initiator composition (C): TBB A type, i.e. partial oxidation tri butyl boron 80 weight portion, hexane 19 weight portion, ethanol 1 weight portion

(viscosity evaluation)

According to following table 1 embodiment 1A ~ 9A described in proportioning, weigh polymer (B) in sample cell, the monomer (A) mix the proportioning described in the same embodiment 1A according to following table 1 ~ 9A in sample cell separately and polymerization initiator composition (C) inject the sample cell that weighing has polymer (B), mix at 25 DEG C, prepare adhesive composition of the present invention or wound coating composition, measure the preparation viscosity of latter 30 seconds.It should be noted that, viscosity is more than 0.4cp in the preparation, and confirm viscosity through time rise.Viscosity uses E type viscometer (Tokyo gauge (strain) is made, EHP type) 25 DEG C of mensuration.Evaluation result is as shown in table 1.

(evaluation of coating)

According to following table 1 embodiment 1A ~ 9A described in proportioning, polymer (B) is weighed in the syringe in luer portion with cap, proportioning mixed monomer (A) and polymerization initiator composition (C) in sample cell that the same embodiment 1A according to following table 1 ~ 9A records are injected in said syringe, mixes at 25 DEG C.Then, take off the cap of syringe, the nozzle of wide 1cm, thick 1mm is installed, the compositions 1ml of mixing is coated on polyethylene film-making material with the length of 4cm.Evaluate point 1 ~ 5 Pyatyi, that is, coating material width be more than 1cm less than 1.2cm be 5, more than 1.2cm less than 1.4cm be 4, more than 1.4cm less than 1.6cm be 3, more than 1.6cm be 2, what can not be coated with is 1, and evaluation result is as shown in table 1.

And confirm following situation: in the adhesive composition containing above-mentioned (A), (B) and (C) or wound coating composition, viscosity after 30 seconds is less than to the compositions of 0.4cp, coating material width is too large, and, for the viscosity after 30 seconds more than the said composition of 75000cp, syringe can not be used to be coated with.

[table 1] table 1

(making of the film (film) of polymerizing curable)

According to following table 2 embodiment 10A ~ 13A described in proportioning, polymer (B) is weighed in 5ml sample cell, proportioning described in the same embodiment 10A according to following table 2 ~ 13A is joined above-mentioned weighing by monomer liquid (A) prepared by 1ml sample cell with the mixed liquor of polymerization initiator composition (C) separately to be had in the sample cell of polymer (B), then, using Glass rod to mix at 25 DEG C makes it even in about 5 seconds.

The adhesive composition obtained or wound coating composition are injected in syringe, as shown in Figure 1, in accordance with the following steps, are filled in immediately in mold frame and make sample film.

On a glass according to the superimposed placement of order of the fluororesin molding jig framework (mold frame inside dimension: long 25mm × wide 2mm) of the sheet material of PE Lumirror (trade mark), thick 0.5mm.The adhesive composition produced or wound coating composition is filled in this mold frame.Attention operation makes not to be mixed into bubble when filling.After end-of-fill, thereon further according to the sheet material of PE Lumirror (trade mark), the superimposed placement of order of glass plate, fix outside 2 glass sheets with clip 4 jiaos.Then, under 25 DEG C (room temperature), leave standstill 24 hours, then, take out film from mold frame.When the surface of the film obtained exists concavo-convex, concavo-convex with the removing of water-proof abrasive paper 600# lapped face, make sample film.The sample film obtained is of a size of: long 25mm, wide 2mm, thick 0.5mm.

The modulus of elasticity in static bending (test speed 2mm/ minute), the tensile elongation (test speed 1mm/ minute) (the SS characteristic of film) of this sample film use Inc. of Shimadzu Seisakusho Ltd. EzTest/CE to obtain.It should be noted that, the SS characteristic value of above-mentioned film is the meansigma methods of the value measured by 4 sample film.Evaluation result is as shown in table 2.

[table 2] table 2

(embodiment 14A ~ 17A) (using the evaluation of the bonding strength of Yucatan miniature pig (YMP) skin)

According to following table 3 embodiment 14A ~ 17A described in proportioning, polymer (B) is weighed in 5ml sample cell, add equally according to following table 3 embodiment 14A ~ 17A described in the monomer (A) prepared with 1ml sample cell separately of proportioning and the mixture of polymerization initiator composition (C), then, using Glass rod to mix at 25 DEG C makes it even in about 5 seconds.

The compositions obtained is injected syringe, as shown in Figure 2, in accordance with the following steps, makes bonding strength assess sample.On a glass, place the sheet material of PE Lumirror (trade mark), peel off fatty tissue also with the YMP skin (crust is in upside) of the 2cm × 2cm of 70% ethanol water defat, the mold frame engraving the Fluororesin sheet of the thick 0.5mm of the positive round (area 18.1 squares of mm) of diameter 4.8mm, to in the mold frame of this Fluororesin sheet, fill the adhesive composition shown in embodiment 14A ~ 17A or wound coating composition.Attention operation makes not to be mixed into bubble when filling.After end-of-fill, superimposed placement YMP skin (crust is in downside), PE Lumirror (trade mark) sheet material, glass plate in order thereon, applies the load of about 150g, leaves standstill 24 hours room temperature about 25 DEG C.Then, removing both sides glass plate, PE Lumirror (trade mark), obtain the assess sample of bonding strength.For above-mentioned sample, obtain pulling force (test speed 1mm/ minute), bonding strength with Inc. of Shimadzu Seisakusho Ltd. EzTest/CE.They are meansigma methodss of the value by 4 test films mensuration.The evaluation result measured according to the method described above is shown in table 3.

[table 3] table 3

(embodiment 18A) (using the evaluation organizing hazardness of Cavia porcellus)

3cm ~ 4cm is cut under anaesthesia on the skin of Hartley class guinea pig back carrying out 5 week age of shaving hair and defeathering.According to table 4 embodiment 18A described in proportioning, polymer (B) is weighed in outlet with cap and close syringe in.Similarly, the proportioning recorded according to embodiment 18, mix monomer (A) and polymerization initiator composition (C) in sample cell, inject this mixed liquor and be equipped with in the syringe of above-mentioned polymer (B), mix at 25 DEG C.Then, take off the cap of the syringe that (A) (B) (C) 3 composition is housed, the nozzle of peristome with wide 1cm, thick 1mm is installed, while the nozzle opening portion of the adhesive composition be mixed with by syringe is extruded within 10 seconds, coat and press with finger closed Cavia porcellus cut wound.

In enforcement operation after 30 minutes, after 2 hours, after 6 hours, after 24 hours, after 72 hours, after 168 hours, investigation wound character, redness, swelling degree, then make animal euthanasia, cut the skin of coating part 1cm × 1cm, fix with formalin.Then, make tissue slice according to usual method, carry out hematoxylin-eosin staining, use observation by light microscope.

As a result, skin properties is no problem, also unconfirmed to rubescent and swelling.In addition, in tissue slice is observed, the inflammation caused by coating arriving adhesive composition or wound coating composition unconfirmed, unconfirmed to the harmfulness to skin histology.

[table 4] table 4

(embodiment 1B ~ 7B, reference example 1B ~ 4B)

In following embodiment and comparative example, use the monomer (A) same with above-described embodiment, polymer (B), polymerization initiator composition (C).In addition, use following material as polymerization inhibitor (D).

Polymerization inhibitor (D): Hydroquinone monomethylether

This polymerization inhibitor is dissolved in monomer (A) according to the amount that following table 5, table 6 and table 7 are recorded.

(evaluation of coating)

Polymer (B) 1156mg (40.0 weight portion) is weighed in outlet with cap and close syringe in, mixing, monomer (A) 1680mg (58.1 weight portion) being dissolved with the polymerization inhibitor (D) of the amount (relative to monomer (A)) described in the embodiment 1B ~ 3B of following table 5 and reference example 1B, 2B and polymerization initiator composition (C) 54mg (1.9 weight portion) to be weighed in sample cell and after being mixed, be injected in the above-mentioned syringe that polymer (B) is housed, mix at 25 DEG C.Then, take off the cap of the syringe that (A) (B) (C) 3 composition is housed, mounting opening is the nozzle of wide 1cm, thick 1mm, is coated on polyethylene film-making material by the adhesive composition 1ml of mixing with the length of 4cm.Evaluate point 1 ~ 5 Pyatyi, that is, the width of coating material be more than 1cm less than 1.2cm be 5, more than 1.2cm less than 1.4cm be 4, more than 1.4cm less than 1.6cm be 3, more than 1.6cm be 2, what can not be coated with is 1.Evaluation result is as shown in table 5.

(evaluation of hardening time)

Polymer (B) 1156mg (40.0 weight portion) is weighed in the syringe of also closing with cap in outlet, mixing, monomer (A) 1680mg (58.1 weight portion) being dissolved with the polymerization inhibitor (D) of the amount (relative to monomer (A)) described in the embodiment 1B ~ 3B of following table 5 and reference example 1B, 2B and polymerization initiator composition (C) 54mg (1.9 weight portion) to be weighed in sample cell and after being mixed, be injected in the above-mentioned syringe that polymer (B) is housed, mix at 25 DEG C.Then, take off the cap of the syringe that (A) (B) (C) 3 composition is housed, the nozzle of wide 1cm, thick 1mm is installed, the adhesive composition 1ml of mixing is coated on polyethylene film-making material with the length of 4cm.Then, keeping under the state that adhesive composition is constant, using fluororesin system rod contact coating material surface, investigate the time becoming do not adhere (wire drawing), using this time as hardening time.Evaluation result is as shown in table 5.

[table 5] table 5

	Polymerization inhibitor (D) (ppm)	Coating	Hardening time (second)
				Reference example 1B	0	1	0
Embodiment 1B	10	5	5
				Embodiment 2B	200	5	60
Embodiment 3B	5000	3	750
				Reference example 2B	10000	2	1800

(evaluation of storage stability)

To dissolve and monomer (A) 3000mg being mixed with the polymerization inhibitor (D) of the embodiment 4B ~ 6B of following table 6 and the amount (relative to monomer (A)) described in reference example 3B, 4B weighs in the sample cell of 5ml, preserve 10 days in the thermostat of 60 DEG C.Open sample cell after 10 days, investigate and whether solidify.Evaluation result is as shown in table 6.

[table 6] table 6

	Polymerization inhibitor (D) (ppm)	Storage stability
			Reference example 3B	0	There is solidification
Embodiment 4B	100	Uncured
			Embodiment 5B	200	Uncured
Embodiment 6B	5000	Uncured
			Reference example 4B	10000	Uncured

(employing the evaluation organizing hazardness of Cavia porcellus)

3cm ~ 4cm is cut under anaesthesia on the skin of Hartlay class guinea pig back carrying out 5 week age of shaving hair and defeathering.According to table 7 embodiment 7B described in proportioning, polymer (B) is weighed in luer portion with in the syringe of cap.Similarly, the proportioning recorded according to the embodiment 7 of table 7, is injected in said syringe by the monomer (A) and polymerization initiator composition (C) that are mixed with polymerization inhibitor (D) in sample cell, mixes at 25 DEG C.Then, take off the cap of syringe, mounting opening is the nozzle of wide 1cm, thick 1mm, and the adhesive composition of mixing is coated above-mentioned cut.In enforcement operation after 30 minutes, after 2 hours, after 6 hours, after 24 hours, after 72 hours, after 168 hours, confirm skin properties, with or without rubescent, with or without swelling, then make animal euthanasia, cut the skin of coating part 1cm × 1cm, fix with formalin.Then with H-E dyeing, above-mentioned fixing sample is dyeed, the tissue slice microscope made is observed.

As a result, skin properties is no problem, also unconfirmed to rubescent and swelling.In addition, in the observation of tissue slice, unconfirmed to the inflammation caused by adhesive composition coating, unconfirmed to the harmfulness to skin histology.

[table 7] table 7

(embodiment 1C ~ 31C, comparative example 1C ~ 4C)

In following embodiment and comparative example, use the monomer (A) same with above-described embodiment, polymerization initiator composition (C).As polymer (B), the proportioning recorded with following table 8 is used to mix above-mentioned polymer (b1), (b2), (b3) and the material that formed.

(viscosity evaluation)

According to the embodiment 1C of following table 8 ~ 13, embodiment 3C, embodiment 4C, embodiment 9C, embodiment 10C, embodiment 15C, embodiment 17C, embodiment 19C, embodiment 22C, embodiment 23C, proportioning described in embodiment 27C, polymer (B) is weighed in luer portion with the HENKE SASS WOLF Inc. 5ml of the plastic cap of Osaka Chemical Inc. with luer lock without in latex (latex-free) syringe, the monomer (A) mix the same proportioning recorded according to above-described embodiment in 10ml glass sample preparation QC and polymerization initiator composition (C) are injected in said syringe, with hands fierceness vibration 20 seconds at 25 DEG C, be uniformly mixed thus.Then, take off the cap of syringe, the entry needle of Terumo Inc. 18G is installed, use flow graph (HAAKE Inc., RS150) at 35 DEG C, measure the viscosity of preparation after latter 60 seconds.It should be noted that, viscosity is more than 0.4cp in the preparation, confirm viscosity through time rise.Evaluation result is as shown in table 8 ~ 15.

(deliquescent evaluation)

According to following table 8 ~ 15 embodiment 1C ~ 31C, comparative example 1C ~ 4C described in proportioning, polymer (B) is weighed in luer portion with the HENKE SASS WOLF Inc. 5ml of the plastic cap of Osaka Chemical Inc. with luer lock without latex syringe, the monomer (A) mix the same proportioning recorded according to embodiment 1C ~ 31C, comparative example 1C ~ 4C in 10ml glass sample preparation QC and polymerization initiator composition (C) are injected in said syringe, at 25 DEG C, within 20 seconds, make it be uniformly mixed with the vibration of hands fierceness.Then, the state of the mixture in visual confirmation syringe.Evaluate and carry out as follows: unconfirmedly will arrive the situation of powder of polymer (B) as 3, using situation about slightly confirming as 2, using situation about confirming in a large number as 1.Evaluation result is as shown in table 8 ~ 15.

(evaluation of coating)

According to following table 8 ~ 15 embodiment 1C ~ 31C, comparative example 1C ~ 4C described in proportioning, polymer (B) is weighed in the HENKE SASS WOLF Inc. 5ml syringe in luer portion with the plastic cap of Osaka Chemical Inc., the same monomer (A) that mixes in sample cell according to the proportioning described in embodiment 1C ~ 31C, comparative example 1C ~ 4C and polymerization initiator composition (C) are injected in said syringe, at 25 DEG C, within 20 seconds, make it mix with hands intense vibration.Then, take off the cap of syringe, mounting opening is the nozzle of wide 1cm, thick 0.5mm, is coated on polyethylene film-making material by the compositions 1ml of mixing with the length of 4cm.Evaluate and carry out as follows: about extruding from container, situation about can easily extrude is as 3, and using both hands, firmly extrudable situation is as 2, and situation about can not extrude is as 1, in addition, sprawling about coating material, what the width of coating material was more than 1cm less than 1.2cm be 5, more than 1.2cm is 4 less than 1.4cm, more than 1.4cm is 3 less than 1.6cm, more than 1.6cm less than 1.8cm be 2, more than 1.8cm less than 3cm be 1, more than 3cm be 0.Evaluation result is as shown in table 8 ~ 15.

(being polymerized and the making of film (film) after solidifying)

According to the embodiment 1C of following table 8 ~ 13, embodiment 3C, embodiment 4C, embodiment 10C, embodiment 15C, embodiment 17C, embodiment 19C, embodiment 22C, embodiment 23C, embodiment 27C, proportioning described in embodiment 28C, polymer (B) is weighed in luer portion with the HENKE SASS WOLF Inc. 5ml of the plastic cap of Osaka Chemical Inc. with luer lock without in latex syringe, will be same according to embodiment 1C, embodiment 3C, embodiment 4C, embodiment 10C, embodiment 15C, embodiment 17C, embodiment 19C, embodiment 22C, embodiment 23C, embodiment 27C, the monomer (A) that the proportioning that embodiment 28C records mixes in sample cell and polymerization initiator composition (C) are injected in said syringe, at 25 DEG C, intense vibration makes it mix in 20 seconds.Then, as shown in Figure 1, in accordance with the following steps, mold frame is filled in immediately to make sample film.On a glass with the superimposed placement of order of the fluororesin molding jig framework of PE Lumirror (trade mark) sheet material, thick 0.5mm (mold frame inside dimension: long 25mm × wide 2mm).Adhesive composition or the wound coating composition of making is filled in this mold frame.Attention operation makes not to be mixed into bubble when filling.After end-of-fill, thereon further according to the sheet material of PE Lumirror (trade mark), the superimposed placement of order of glass plate, fix outside two glass sheets with clip 4 jiaos.Then, under 25 DEG C (room temperature), leave standstill 24 hours, then, from mold frame, take out film.When the surface of the film obtained exists concavo-convex, concavo-convex with the removing of water-proof abrasive paper 600# lapped face, make sample film.The sample film obtained is of a size of: long 25mm, wide 2mm, thick 0.5mm.

The modulus of elasticity in static bending (test speed 2mm/ minute), the tensile elongation (test speed 1mm/ minute) of this sample film is tried to achieve with Autograph (Inc. of Shimadzu Seisakusho Ltd. EZ-S).It should be noted that, the modulus of elasticity in static bending of this film and the value of tensile elongation are the meansigma methodss of the value by 4 sample film mensuration.Evaluation result is as shown in table 8 ~ table 13.

(using the evaluation of the bonding strength of YMP skin)

Use YMP Corii Sus domestica (Japanese Charles River (strain) Inc.), test based on ASTM F2255-05.Namely, as shown in Figure 3, by removing fat deposit, the YMP skin of thick 2 ~ 3mm made cuts into 25mm (wide) × 20 (length) mm, behind paper using wiping two sides, is alignd in the width of 25mm one end with the acrylic panel (acrylic plate) of 25mm (wide) × 80mm (length), corium side, upper, is attached at acrylic panel with East Asia synthesis (strain) Inc. Aron Alpha (trade mark) by crust.Then, longitudinal direction Teflon cream (trade mark) being coated distance acrylic panel holds skin (crust) and the skin side of long more than 10mm, and regulation " coated face (25mm (wide) × 10mm (length)) of binding agent " forms adherend.Be used in the gauze soaked in normal saline and wrap up this adherend, and loaded hermetic container, at 37 DEG C, be incubated 30 minutes.Then, according to following table 8, the embodiment 1C of table 11, embodiment 3C, embodiment 4C, proportioning described in embodiment 17C, polymer (B) is weighed in luer portion with the HENKE SASS WOLF Inc. 5ml of the plastic cap of Osaka Chemical Inc. with luer lock without latex syringe, will be same according to embodiment 1C, embodiment 3C, embodiment 4C, the monomer (A) that the proportioning that embodiment 17C records mixes in sample cell and polymerization initiator composition (C) inject in said syringe, within 20 seconds, mixed with the vibration of hands fierceness at 25 DEG C, thus produce adhesive composition or wound coating composition, above-mentioned adhesive composition or wound coating composition are coated the coated face (25mm × 10mm) of above-mentioned binding agent.Make two panels, the coated face of binding agent is coincided with one another, apply the counterweight of 140g, leave standstill 1 hour.Then, be used in the gauze parcel soaked in normal saline, be stored in container, then at 37 DEG C, leave standstill 24 hours, make bonding strength assess sample.

With test speed 5mm/ minute, tension test is carried out to above-mentioned assess sample with Autograph (Shimadzu Seisakusho Ltd.'s (strain) Inc. EZ-S), obtain the meansigma methods of the value that use 4 test films measure as bonding strength.Evaluation result is as shown in table 8, table 11.

(overall merit)

Dissolubility and coating (extruding from container, sprawling of coating material) evaluation be more than 3 for AA, dissolubility and coating (extruding from container, sprawling of coating material) evaluation be more than 2 for A, dissolubility and coating (extruding from container) be evaluated as more than 2 and the evaluation of coating (sprawling of coating material) is more than 1 for B, the situation that dissolubility is 1, coating (extruding from container) is 1, coating (sprawling of coating material) is 0 is C.Evaluation result is as shown in table 8 ~ 15.

[embodiment 32C ~ 34C, comparative example 5C]

(using the evaluation organizing hazardness of rat)

With pentobarbital sodium anesthesia electric hairdressing device, back was carried out to male Crl:CD (SD) rat (SPF, Japanese Charles River (strain)) in 11 week age of shaving hair process, with alcohol swab, skin was carried out disinfection.According to table 16 embodiment 32C ~ 34C described in proportioning, polymer (B) is weighed in luer portion with the HENKE SASS WOLF Inc. 5ml of the plastic cap of Osaka Chemical Inc. with luer lock without in latex syringe, the monomer (A) mix the proportioning that the same embodiment 32C according to table 16 ~ 34C records in 10ml glass sample preparation QC and polymerization initiator composition (C) inject in said syringe, at 25 DEG C, within 20 seconds, make it be uniformly mixed with the vibration of hands fierceness.After mixing, take off above-mentioned plastic cap, entry needle (18G) is installed, after the air fully in removing syringe, to dorsal sc (between corium and subcutaneous fat) administration 400 μ L.As comparative example, give Dermabond (trade mark) (Johnson & Johnson K.K. system) the 400 μ L of cyanoacrylate skin binding agent.It should be noted that, give normal saline 400 μ L as negative control.

Administration, after 72 hours and 168 hours, after making above-mentioned rat euthanasia, extracts above-mentioned skin, fixes with formalin under the hair of the skin of back keeping subcutaneous administration position does not shave the state removed.After fixing, make wax embedding block, carry out hematoxylin-eosin (H-E) dyeing (lymphocyte dyeing), congo red staining (acidophil dyeing) and Toluidine blue staining (mastocyte dyeing), use microscopic examination.Pathological discovery is used tricks a point standard (0: without finding, 1: slight, 2: slight, 3: moderate, 4: highly) evaluate.Evaluation result is shown in table 16.

As a result, confirm because Dermabond (trade mark) contacts with subcutaneous tissue and moderate inflammation occurs, on the other hand, when this adhesive composition or wound coating composition, almost unconfirmed to inflammation.Thus, confirm above-mentioned composition and for skin histology, there is high security as skin binding agent or wound coating agent.

(using the healing of the cut of rat to confirm)

Carry out shaving hair with after the male SD rat in 5 week age of anaesthetized with pentobarbital, from apart from xiphoid-process 5mm place towards the otch of the transdermal of afterbody formation 30mm.According to table 16 embodiment 34C described in proportioning, polymer (B) is weighed in luer portion with the HENKE SASS WOLF Inc. 5ml of the plastic cap of Osaka Chemical Inc. with luer lock without in latex syringe, the monomer (A) that the proportioning recorded by the same embodiment 34C according to table 16 mixes in 10ml glass sample preparation QC and polymerization initiator composition (C) are injected in said syringe, at 25 DEG C, within 20 seconds, make it be uniformly mixed with the vibration of hands fierceness.Then, take off above-mentioned plastic cap, mounting opening is the nozzle of wide 1cm, thick 1mm, after gauze hemostasis, and compressive engagement face coating adhesive 500 μ L on one side securely.Implement operation 1,2 weeks, after 3 months, make above-mentioned rat euthanasia, gather the abdominal tissues (skin and subcutaneous tissue) of long 3cm × wide 2cm size, fix with formalin.After fixing, make wax embedding block, carry out H-E dyeing, evaluate healing degree by microscopic examination.

Confirm the situation of 1 week, 2 weeks and 3 months, the cut of the coated above-mentioned skin binding agent of results verification or wound coating composition does not have different from the tissue do not cut, and is fully cured.

Symbol description

11: glass plate 12:Lumirror (trade mark) 13: fluororesin mold frame (central white portion illustrates the space of long 25mm × wide 2mm, hitherward filling adhesive compositions or wound coating composition)

21: glass plate 22:Lumirror (trade mark) 23:YMP skin (crust is in downside) 24: fluororesin mold frame (central white portion illustrates the positive round of diameter 4.8mm, hitherward filling adhesive compositions or wound coating composition)

31:Teflon cream coating part 32:YMP skin (crust is in upside) 33: acrylic panel

Claims (16)

1. a soft tissue adhesive composition, the coating adhesive composition of wound or wound coating composition, for containing (methyl) acrylate as monomer (A), (methyl) acrylate polymer as polymer (B) and containing as the adhesive composition of the polymerization initiator composition (C) of the partial oxidation tri butyl boron of organoboron compound, the coating adhesive composition of wound or wound coating composition

Described (A), (B) and (C) mix the viscosity of latter 60 seconds 100 ~ 1, in the scope of 000,000cp,

Relative to monomer (A), polymer (B) and polymerization initiator composition (C) 100 weight portion, in the scope of polymer (B) more than 28 weight portions below 55 weight portions, the addition of above-mentioned polymerization initiator composition (C) is 0.5 ~ 10 weight portion

Described polymer (B) is the polymeric blends containing following composition:

Relative to the gross weight of polymer particle (b1), (b2) and (b3), polymer particle (b2) containing more than 2 % by weight and polymer particle (b3), less than 10 ~ 60 % by weight polymer particle (b1), the weight average molecular weight of polymer particle (b2) is 5 × 10 ⁴~ 20 × 10 ⁴and specific surface area is 0.51 ~ 1.2m ²/ g, the weight average molecular weight of polymer particle (b3) is 5 × 10 ⁴~ 20 × 10 ⁴and specific surface area is 0.1 ~ 0.5m ²/ g, the weight average molecular weight of polymer particle (b1) is 30 × 10 ⁴~ 60 × 10 ⁴and specific surface area is 1.5 ~ 4.5m ²/ g, wherein, the total amount of (b1), (b2) and (b3) is 100 % by weight.

2. soft tissue adhesive composition, the coating adhesive composition of wound or wound coating composition as claimed in claim 1, it is characterized in that, prepare adhesive composition according to claim 1 or wound coating composition, thick more than 0.1 μm that is obtained by the described compositions after 24 hours, long more than 25mm and the film of wide more than 2mm, modulus of elasticity in static bending when measuring under the condition of test speed 2mm/ minute is below 750MPa, and tensile elongation when measuring under the condition of test speed 1mm/ minute is more than 5%.

3. soft tissue adhesive composition, the coating adhesive composition of wound or wound coating composition as claimed in claim 1, wherein, also containing polymerization inhibitor (D).

4. soft tissue adhesive composition, the coating adhesive composition of wound or wound coating composition as claimed in claim 3, relative to monomer (A), the content of described polymerization inhibitor (D) is 10 ~ 5000ppm.

5. the coating adhesive composition of the soft tissue adhesive composition as described in claim 3 or 4, wound or wound coating composition, wherein, described polymerization inhibitor (D) is for being selected from hydroquinone, dibutyl hydroquinone, Hydroquinone monomethylether, 2, at least one in 6-DI-tert-butylphenol compounds, 2,6 ditertiary butyl p cresol, catechol, 1,2,3,-thrihydroxy-benzene, benzoquinone, 2-hydroxyl benzoquinone, p methoxy phenol, tert-butyl catechol, butylated hydroxyanisol, Yoshinox BHT and tertiary butylated hydroquinone.

6. the coating adhesive composition of the soft tissue adhesive composition according to any one of Claims 1 to 4, wound or wound coating composition, wherein, also containing UV absorbent.

7. the coating adhesive composition of the soft tissue adhesive composition according to any one of Claims 1 to 4, wound or wound coating composition, wherein, also containing plasticizer.

8. the soft tissue adhesive composition according to any one of Claims 1 to 4, the coating adhesive composition of wound, or wound coating composition, wherein, also containing at least one be selected from following substances: anti-infective, antibiotic, antibacterial, antiviral agent, analgesic, the coordination compound of analgesic, appetite suppressant, vermifuge, anti-arthritic, anti-asthmatic, spasmolytic, antidepressants, antidiuretic, diarrhea, antihistaminic, anti-inflammatory agent, migraine medicament, antiemetic, antineoplastic agent, antiparkinsonism drug, antipruritic, psychosis, antipyretic, anti-spasmodics, anticholinergic, sympathetic activation agent, cardiovascular drugs agent, anti-arrhythmic, antihypertensive, diuretic, vasodilation, immunosuppressant, muscle relaxant, parasympatholytic, analeptic, tranquilizer, spiritual stability agent, cholinomimetic, chemotherapeutics, radiopharmaceutical, self-bone grafting medicine, the heparin nertralizer of bladder quiescence, coagulant, hemorrhage, xanthine derivative, hormone, natural origin or the protein synthesized by genetic engineering, polysaccharide, glycoprotein, lipoprotein, oligonucleotide, antibody, antigen, vassopressin, vassopressin analog, epinephrine, select albumen, the courageous and upright poisonous substance of coagulant, plasminogen activator inhibitor, platelet activating agent, and there is the synthetic peptide of anastalsis, and as the orange oil of spice, Oleum Citri grandis, Fructus Citri Limoniae oil, white lemon oil, Oleum Caryophylli, wintergreen oil, Oleum menthae, peppermint spirit, Fructus Musae distillation, Fructus Cucumidis sativi distillation, Mel distillation, rose water, menthol, anethole, alkyl salicylate, benzaldehyde, monosodium glutamate, ethyl vanillin, thymol, and vanillin.

9. a soft tissue binding agent, the coating binding agent of wound, or wound coating agent test kit, have as lower member: by soft tissue adhesive composition according to claim 1, the coating adhesive composition of wound, or (methyl) acrylate as monomer (A) contained in wound coating composition, as (methyl) acrylate polymer of polymer (B), and be divided into more than two parts and the component they received containing polymerization initiator composition (C) each composition as the partial oxidation tri butyl boron of organoboron compound with combination in any.

10. soft tissue binding agent, the coating binding agent of wound or wound coating agent test kit as claimed in claim 9, it is characterized in that, there is following formation: monomer (A), polymer (B) and polymerization initiator composition (C) are independently received, first monomer (A) and the polymerization initiator composition (C) containing organoboron compound are mixed, then mixed polymer (B).

11. 1 kinds of soft tissue binding agents, the coating binding agent of wound, or wound coating agent test kit, have as lower member: by soft tissue adhesive composition according to claim 3, the coating adhesive composition of wound, or (methyl) acrylate as monomer (A) contained in wound coating composition, (methyl) acrylate polymer (B), containing the polymerization initiator composition (C) as the partial oxidation tri butyl boron of organoboron compound, and polymerization inhibitor (D) each composition is divided into more than two parts with combination in any and the component they received.

12. soft tissue binding agents as claimed in claim 11, the coating binding agent of wound or wound coating agent test kit, it is characterized in that, there is following formation: the mixture of monomer (A) and polymerization inhibitor (D), polymer (B) and polymerization initiator composition (C) are independently received, first monomer (A) is mixed with the mixture of polymerization inhibitor (D) and the polymerization initiator composition (C) containing organoboron compound, then mixed polymer (B).

13. soft tissue binding agent, the coating binding agent of wound or wound coating agent test kits according to any one of claim 9 ~ 12, wherein, the instrument used when comprising the following compositions of coating, described compositions is that the adhesive ingredients containing described (A), (B), (C) and (D) or wound coating agent composition are maybe mixed to get by the compositions adhesive ingredients containing described (A), (B) and (C) or wound coating agent composition are obtained by mixing.

14. soft tissue binding agents as claimed in claim 13, the coating binding agent of wound or wound coating agent test kit, wherein, described instrument is be selected from least one in pen, fibrous nodules, cloth, sponge ball, sponge sheet.

15. soft tissue binding agent, the coating binding agent of wound or wound coating agent test kits according to any one of claim 9 ~ 12,14, wherein, the bonding pre-treatment aqueous solution containing the citric acid of 1 ~ 15 % by weight, the iron chloride (III) of 1 ~ 5 % by weight is also comprised.

16. soft tissue binding agents as claimed in claim 13, the coating binding agent of wound or wound coating agent test kit, wherein, the bonding pre-treatment aqueous solution containing the citric acid of 1 ~ 15 % by weight, the iron chloride (III) of 1 ~ 5 % by weight is also comprised.